Cited by 239BRCA gene mutations in cancerRNA Research and SplicingGenomics and Rare Diseases

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Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants

Houdayer, Claude, Caux-Moncoutier, Virginie, Krieger, Sophie, Barrois, Michel, Bonnet, Françoise, Bourdon, Violaine, Bronner, Myriam, Buisson, Monique, Coulet, Florence, Gaildrat, Pascaline, Lefol, Cédrick, Léone, Mélanie, Mazoyer, Sylvie, Muller, Danielle, Remenieras, Audrey, Révillion, Françoise, Rouleau, Etienne, Sokolowska, Joanna, Vert, Jean-Philippe, Lidereau, Rosette, Soubrier, Florent, Sobol, Hagay, Sevenet, Nicolas, Bressac-de Paillerets, Brigitte, Hardouin, Agnès, Tosi, Mario, Sinilnikova, Olga M., Stoppa-Lyonnet, Dominique·2012·Human Mutation

DOI 10.1002/humu.22101

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Abstract

Assessing the impact of variants of unknown significance (VUS) on splicing is a key issue in molecular diagnosis. This impact can be predicted by in silico tools, but proper evaluation and user guidelines are lacking. To fill this gap, we embarked upon the largest BRCA1 and BRCA2 splice study to date by testing 272 VUSs (327 analyses) within the BRCA splice network of Unicancer. All these VUSs were analyzed by using six tools (splice site prediction by neural network, splice site finder (SSF), MaxEntScan (MES), ESE finder, relative enhancer and silencer classification by unanimous enrichment, and human splicing finder) and the predictions obtained were compared with transcript analysis results. Combining MES and SSF gave 96% sensitivity and 83% specificity for VUSs occurring in the vicinity of consensus splice sites, that is, the surrounding 11 and 14 bases for the 5' and 3' sites, respectively. This study was also an opportunity to define guidelines for transcript analysis along with a tentative classification of splice variants. The guidelines drawn from this large series should be useful for the whole community, particularly in the context of growing sequencing capacities that require robust pipelines for variant interpretation.

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Listening to silence and understanding nonsense: exonic mutations that affect splicing
Cartegni, L., Chew, S. L., & Krainer, A. R. (2002) · Nature Reviews Genetics · doi:10.1038/nrg775 · Cited by 2,209
Intronic variants in BRCA1 and BRCA2 that affect RNA splicing can be reliably selected by splice-site prediction programs
Vreeswijk, M. P. G., Kraan, J. N., van der Klift, H. M., Vink, G. R., Cornelisse, C. J., Wijnen, J. T., Bakker, E., van Asperen, C. J., & Devilee, P. (2009) · Human Mutation · doi:10.1002/humu.20811 · Cited by 98

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Items 101–200 of 227

Usefulness and Limitations of Comprehensive Characterization of mRNA Splicing Profiles in the Definition of the Clinical Relevance of BRCA1/2 Variants of Uncertain Significance
Gelli, E., Colombo, M., Pinto, A. M., Vecchi, G. D., Foglia, C., Amitrano, S., Morbidoni, V., Imperatore, V., Manoukian, S., Baldassarri, M., et al. (2019) · Cancers · doi:10.3390/cancers11030295 · Cited by 25
“However, their predictions have been demonstrated to be highly reliable for variants located in Cartegni-consensus regions, but less accurate for variants lying in elements such as the exonic splicing enhancer (ESE) or branchpoints [19].”
BackgroundInfluential
Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next‐generation sequencing
Hannan, F. A., Keogh, M. B., Taha, S., & Buainain, L. A. (2019) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.771 · Cited by 21
“The second detected heterozygous BRCA2 c.67+2T>C variant is located 2 nucleotide downstream of intron 2; The BRCA2 c.67+2T>C splice‐site variant has been previously identified as a pathogenic mutation and already described in the BIC database (Diez et al., 2003; Houdayer et al., 2012).”
Background
Molecular characterization and clinical interpretation of BRCA1/BRCA2 variants in families from Murcia (south-eastern Spain) with hereditary breast and ovarian cancer: clinical–pathological features in BRCA carriers and non-carriers
Barrios, X. G., Meseguer, M. D. S., Vera, M. M., Bermúdez, A. I. S., Cerrolaza, J. A. M., Henarejos, P. S., Poves, M. Z., Hernández, M. G. G., Tortosa, E. C., Baño, Á. A., et al. (2017) · Familial Cancer · doi:10.1007/s10689-017-9985-x · Cited by 21
“[14] and, for interpretation of splicing variants and aberrations, we used the list of variants described in ENIGMA Consortium (Enigma Splicing Working Group) [15] and the three-level classification system (1S, 2S and 3S) in Houdayer et al [16].”
Method
BRCA1/2 variants of unknown significance in hereditary breast and ovarian cancer (HBOC) syndrome: Looking for the hidden meaning
Fanale, D., Pivetti, A., Cancelliere, D., Spera, A., Bono, M., Fiorino, A., Pedone, E., Barraco, N., Brando, C., Perez, A., et al. (2022) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2022.103626 · Cited by 21
A practical guide to interpreting germline variants that drive hematopoietic malignancies, bone marrow failure, and chronic cytopenias.
Feurstein, S., Hahn, C., Mehta, N., & Godley, L. (2022) · Genetics in Medicine · doi:10.1016/j.gim.2021.12.008 · Cited by 20
Rare germline genetic variants and risk of aggressive prostate cancer
Nguyen‐Dumont, T., MacInnis, R. J., Steen, J. A., Theys, D., Tsimiklis, H., Hammet, F., Mahmoodi, M. S., Pope, B. J., Park, D. J., Mahmood, K., et al. (2020) · International Journal of Cancer · doi:10.1002/ijc.33024 · Cited by 18
Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from 'unknown significance' to 'Likely pathogenic' based on clinical evidence in Korea.
Ryu, J., Kang, G., Nam, S., Kim, S., Yu, J., Lee, S., Bae, S., Park, S., Paik, H., Kim, J.-W., et al. (2017) · Breast · doi:10.1016/j.breast.2017.03.006 · Cited by 20
Systematic analysis of splicing defects in selected primary immunodeficiencies-related genes.
Grodecká, L., Hujová, P., Kramárek, M., Kršjaková, T., Kováčová, T., Vondrášková, K., Ravčuková, B., Hrnčířová, K., Souček, P., & Freiberger, T. (2017) · Clinical Immunology · doi:10.1016/j.clim.2017.03.010 · Cited by 18
Mutation analysis of PALB2 gene in French breast cancer families
Damiola, F., Schultz, I., Barjhoux, L., Sornin, V., Dondon, M.-G., Eon-Marchais, S., Marcou, M., Caron, O., Gauthier-Villars, M., de Pauw, A., et al. (2015) · Breast Cancer Research and Treatment · doi:10.1007/s10549-015-3625-7 · Cited by 18
Self-citation
Characterization of three alternative transcripts of the BRCA1 gene in patients with breast cancer and a family history of breast and/or ovarian cancer who tested negative for pathogenic mutations
Gambino, G., Tancredi, M., Falaschi, E., Aretini, P., & Caligo, M. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2103 · Cited by 18
“Several studies have demonstrated that, due to variations in splice sites, BRCA1/BRCA2 may generate truncated, non-functional proteins that may be associated with a predisposition to breast and ovarian cancer (22).”
Recommendations by the ClinGen Rett/Angelman-like Expert Panel for Gene-specific Variant Interpretation Methods
McKnight, D., Bean, L. J. H., Karbassi, I., Beattie, K., Bienvenu, T., Bonin, H., Fang, P., Chrisodoulou, J., Friez, M., Helgeson, M. L., et al. (2021) · Human Mutation · doi:10.1002/humu.24302 · Cited by 17
“We define significant splicing alterations as ≥15% change to the natural splice site (Houdayer et al., 2012).”
Background
Comprehensive Functional Characterization and Clinical Interpretation of 20 Splice-Site Variants of the RAD51C Gene
Sanoguera-Miralles, L., Valenzuela-Palomo, A., Bueno-Martínez, E., Llovet, P., Díez-Gómez, B., Caloca, M. J., Pérez-Segura, P., Fraile-Bethencourt, E., Colmena, M., Carvalho, S., et al. (2020) · Cancers · doi:10.3390/cancers12123771 · Cited by 17
“Potential spliceogenic variants were selected according to the following criteria: (i) splice site disruption at the AG/GT positions; (ii) important MES score changes (≥15%) [35,74]; (iii) creation of de novo splice sites; (iv) regardless of computer predictions, variants at other conserved positions of the acceptor (…”
Method
Functional Characterization of Putative Novel Splicing Mutations in the Cardiomyopathy-Causing Genes
Millat, G., Lafont, E., Nony, S., Rouvet, I., & Bozon, D. (2015) · DNA and Cell Biology · doi:10.1089/dna.2015.2842 · Cited by 19
“…absence of an RNA-based assay, a combination of in silico and in vitro tests (Vega et al. , 2009; Wilson et al. , 2009; Di Filippo et al. , 2012; Houdayer et al. , 2012; Raynal et al. , 2013; Rimoldi et al. , 2014) was used to evaluate the splicing impact of nine recently identiﬁed nucleotide…”
Functional correction by antisense therapy of a splicing mutation in the GALT gene
Coelho, A. I., Lourenço, S. P., Trabuco, M. C., Silva, M. J., Oliveira, A., Gaspar, A. M. C., Diogo, L. M., de Almeida, I. T., Vicente, J. B., & Rivera, I. A. (2014) · European Journal of Human Genetics · doi:10.1038/ejhg.2014.149 · Cited by 18
The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity
Colombo, M., López‐Perolio, I., Meeks, H., Caleca, L., Parsons, M. T., Li, H., Vecchi, G. D., Tudini, E., Foglia, C., Mondini, P., et al. (2018) · Human Mutation · doi:10.1002/humu.23411 · Cited by 20
“In accordance with previous studies (Houdayer et al., 2012; Jarhelle et al., 2016; Sanz et al., 2010; Thery et al., 2011; Vreeswijk et al., 2009), we observed that this variant leads to a modest increased expression of the transcript lacking exon 3 (∆3) in carriers compared to controls.”
RAD51D Aberrant Splicing in Breast Cancer: Identification of Splicing Regulatory Elements and Minigene-Based Evaluation of 53 DNA Variants
Bueno‐Martínez, E., Sanoguera‐Miralles, L., Valenzuela‐Palomo, A., Lorca, V., Gómez-Sanz, A., Carvalho, S., Allen, J., Infante, M., Pérez‐Segura, P., Lázaro, C., et al. (2021) · Cancers · doi:10.3390/cancers13112845 · Cited by 24
“Potential spliceogenic variants were selected according to the following criteria: (i) MES score changes (>15%) [16,20] and (ii) creation of alternative sites (Table S2).”
Method
Complex consequences of Cantu syndrome SUR2 variant R1154Q in genetically modified mice
Zhang, H., Hanson, A., de Almeida, T. S., Emfinger, C. H., McClenaghan, C., Harter, T., Yan, Z.-H., Cooper, P., Brown, G. S., Arakel, E. C., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.145934 · Cited by 16
“In many genes, exon inclusion/skipping is becoming recognized as a more common consequence of disease mutations than previously assumed (41-43).”
Background
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
Parsons, M. T., Tudini, E., Li, H., Hahnen, E., Wappenschmidt, B., Feliubadaló, L., Aalfs, C. M., Agata, S., Aittomäki, K., Alducci, E., et al. (2019) · Human Mutation · doi:10.1002/humu.23818 · Cited by 144
“…variants (BRCA2 c.516+1G>T and BRCA2 c.7007+1G>C) demonstrating differences between multifactorial likelihood‐based analysis and the current iteration of ENIGMA “rules‐based” qualitative assessment based on mRNA splicing assay data from patient material (Houdayer et al., 2012; Whiley et al., 2011).”
Self-citation
Full-length transcript amplification and sequencing as universal method to test mRNA integrity and biallelic expression in mismatch repair genes
Morak, M., Schaefer, K., Steinke-Lange, V., Koehler, U., Keinath, S., Massdorf, T., Mauracher, B., Rahner, N., Bailey, J., Kling, C., et al. (2019) · European Journal of Human Genetics · doi:10.1038/s41431-019-0472-8 · Cited by 15
Splicing analysis of 26 F8 nucleotide variations using a minigene assay
Jourdy, Y., Frétigny, M., Nougier, C., Négrier, C., Bozon, D., & Vinciguerra, C. (2019) · Haemophilia · doi:10.1111/hae.13687 · Cited by 16
Current and future molecular approaches in the diagnosis of cystic fibrosis
Bergougnoux, A., Taulan-Cadars, M., Claustres, M., & Raynal, C. (2018) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2018.1457438 · Cited by 15
“Aggregates predictions scores of the main in silico tools Relevant only for variants within the consensus splice regions of known exons: not suitable to predict putative creation of splice sites inside the exons Functional assays In vitro assays: minigenes and expression vectors [55] Sequence of interest inserted in a…”
Background
In vitro and in silico evidence against a significant effect of the SPINK1 c.194G>A variant on pre-mRNA splicing
Wu, H., Boulling, A., Cooper, D., Li, Z.-S., Liao, Z., Chen, J.-M., & Férec, C. (2017) · Gut · doi:10.1136/gutjnl-2017-313948 · Cited by 15
Characterization of BRCA1 and BRCA2 variants found in a Norwegian breast or ovarian cancer cohort
Jarhelle, E., Stensland, H. M. F. R., Mæhle, L., & Ghelue, M. V. (2016) · Familial Cancer · doi:10.1007/s10689-016-9916-2 · Cited by 15
Consequences of germline variation disrupting the constitutional translational initiation codon start sites of MLH1 and BRCA2: use of potential alternative start sites and implications for predicting variant pathogenicity
Parsons, M., Whiley, P., Beesley, J., Drost, M., de Wind, N., Thompson, B. A., Marquart, L., Hopper, J., Jenkins, M. A., Brown, M. A., et al. (2013) · Molecular Carcinogenesis · doi:10.1002/mc.22116 · Cited by 15
APPLICATION OF THE ACMG/AMP FRAMEWORK TO CAPTURE EVIDENCE RELEVANT TO PREDICTED AND OBSERVED IMPACT ON SPLICING: RECOMMENDATIONS FROM THE CLINGEN SVI SPLICING SUBGROUPPreprint
Walker, L., de la Hoya, M., Wiggins, G., Lindy, A., Vincent, L., Parsons, M., Canson, D., Bis-Brewer, D. M., Cass, A., Tchourbanov, A., et al. (2023) · medRxiv · doi:10.1101/2023.02.24.23286431 · Cited by 14
Presumed COL4A3/COL4A4 Missense/Synonymous Variants Induce Aberrant Splicing
Deng, H., Zhang, Y., Ding, J., & Wang, F. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.838983 · Cited by 15
“It was suggested to using multiple in silico tools to pinpoint unclassified variants worthy of transcript analyses (20).”
Background
Potentially pathogenic germline CHEK2 c.319+2T>A among multiple early-onset cancer families
Dominguez-Valentin, M., Nakken, S., Tubeuf, H., Vodák, D., Ekstrøm, P. O., Nissen, A. M., Morak, M., Holinski-Feder, E., Martins, A., Møller, P., et al. (2017) · Familial Cancer · doi:10.1007/s10689-017-0011-0 · Cited by 14
Allelic variation of the COMT gene in a despotic primate society: A haplotype is related to cortisol excretion in Macaca fuscata.
Pflüger, L. S., Gutleb, D. R., Hofer, M., Fieder, M., Wallner, B., & Steinborn, R. (2016) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.11.012 · Cited by 14
“Particularly, the prediction of whether or not changes in the intronic 5' and 3′ splice site region affect RNA splicing seems to be relatively straightforward and highly reliable (Houdayer et al., 2012; Théry et al., 2011; Vreeswijk et al., 2009).”
Germline mutations of multiple breast cancer-related genes are differentially associated with triple-negative breast cancers and prognostic factors
Hata, C., Nakaoka, H., Xiang, Y., Wang, D., Yang, A., Liu, D., Liu, F., Zou, Q., Li, W., Zheng, K., et al. (2020) · Journal of Human Genetics · doi:10.1038/s10038-020-0729-7 · Cited by 16
Results of multigene panel testing in familial cancer cases without genetic cause demonstrated by single gene testing
Dominguez-Valentin, M., Nakken, S., Tubeuf, H., Vodák, D., Ekstrøm, P. O., Nissen, A. M., Morak, M., Holinski-Feder, E., Holth, A., Capellá, G., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-54517-z · Cited by 13
Characterization of spliceogenic variants located in regions linked to high levels of alternative splicing: BRCA2 c.7976+5G > T as a case study
Montalban, G., Fraile-Bethencourt, E., López-Perolio, I., Pérez-Segura, P., Infante, M., Durán, M., Alonso-Cerezo, M. C., López-Fernández, A., Díez, O., de la Hoya, M., et al. (2018) · Human Mutation · doi:10.1002/humu.23583 · Cited by 13
Deep intronic variation in splicing regulatory element of the ERCC8 gene associated with severe but long-term survival Cockayne syndrome
Schalk, A., Greff, G., Drouot, N., Obringer, C., Dollfus, H., Laugel, V., Chelly, J., & Calmels, N. (2018) · European Journal of Human Genetics · doi:10.1038/s41431-017-0009-y · Cited by 13
“Variations affecting canonical splice sites or creating an exonic cryptic site can now be predicted with high confidence by in silico tools that evaluate the strength of splice sites [20].”
The intronic BRCA1 c.5407-25T>A variant causing partly skipping of exon 23—a likely pathogenic variant with reduced penetrance?
Høberg-Vetti, H., Ognedal, E., Buisson, A., Vamre, T., Ariansen, S., Hoover, J., Eide, G., Houge, G., Fiskerstrand, T., Haukanes, B., et al. (2020) · European Journal of Human Genetics · doi:10.1038/s41431-020-0612-1 · Cited by 12
Digging deeper into the intronic sequences of the SPINK1 gene
Zou, W.-B., Masson, E., Boulling, A., Cooper, D., Li, Z.-S., Liao, Z., Férec, C., & Chen, J.-M. (2016) · Gut · doi:10.1136/gutjnl-2016-311428 · Cited by 12
Splicing analyses for variants in MMR genes: best practice recommendations from the European Mismatch Repair Working Group
Morak, M., Pineda, M., Martins, A., Gaildrat, P., Tubeuf, H., Drouet, A., Gómez, C., Dámaso, E., Schaefer, K., Steinke-Lange, V., et al. (2022) · European Journal of Human Genetics · doi:10.1038/s41431-022-01106-w · Cited by 11
Self-citation
Intrinsic Disorder and Phosphorylation in BRCA2 Facilitate Tight Regulation of Multiple Conserved Binding Events
Julien, M., Ghouil, R., Petitalot, A., Caputo, S. M., Carreira, A., & Zinn‐Justin, S. (2021) · Biomolecules · doi:10.3390/biom11071060 · Cited by 14
“Figure 7A represents the distribution and significance of missense variants in the French population, including those exhibiting splicing defects, along the BRCA2 gene [89].”
Background
Internal Standardization of the Interpretation and Reporting of Sequence Variants in Hematologic Neoplasms
Mehta, N., He, R., & Viswanatha, D. (2021) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-021-00540-8 · Cited by 11
Effectiveness of integrated interpretation of exome and corresponding transcriptome data for detecting splicing variants of genes associated with autosomal recessive disorders
Yamada, M., Suzuki, H., Shiraishi, Y., & Kosaki, K. (2019) · Molecular Genetics and Metabolism Reports · doi:10.1016/j.ymgmr.2019.100531 · Cited by 11
“We tested whether the abnormal splicing detected using RNA-seq and the SAVNet software could be predicted by the prototypic software tools MaxEntScan (MES) [26] and SpliceSiteFinder-like (SSF) [27], both of which use current knowledge on the base composition of the splice site sequences and can predict aberrant splici…”
BackgroundMethodInfluential
BRCA1 and BRCA2 germline variants in breast cancer patients from the Republic of Macedonia
Jakimovska, M., Kostovska, I. M., Popovska-Jankovic, K., Kubelka-Sabit, K., Karadjozov, M., Stojanovska, L., Arsovski, A., Smichkoska, S., Lazarova, E., Dimitrovska, M. J., et al. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-017-4642-5 · Cited by 11
RNA-based diagnostic studies in genetics: Review and guidance from a multidisciplinary French network
Buisine, M., Bellanné‐Chantelot, C., Calmels, N., Vaché, C., Besnard, T., Cogné, B., Vitobello, A., Piton, A., Martins, A., Gaildrat, P., et al. (2025) · European Journal of Human Genetics · doi:10.1038/s41431-025-01881-2 · Cited by 10
“For this reason, in silico prediction tools for splicing anomalies have been widely used for decades and the French splicing group published guidelines as soon as 2012 with a simple combination of two bioinformatics variation scores MaxEntScan (MES) and Splice Site Finder-like (SSF-like) [5].”
InfluentialSelf-citation
Value of the loss of heterozygosity to BRCA1 variant classification
dos Santos, E. S., Spurdle, A., Carraro, D., Briaux, A., Southey, M., Torrezan, G., Petitalot, A., Leman, R., Lafitte, P., Meseure, D., et al. (2022) · npj Breast Cancer · doi:10.1038/s41523-021-00361-2 · Cited by 10
“In regard to breast cancer samples, LOH was observed in 69% (35) of tumors with a germline PV (51), within which the loss of the wild-type allele was present in 91% (32 of 35) while the overall allelic balance was observed in 31% (16) carrying PVs (Table 2).”
Self-citation
Identification and Characterization of New Alu Element Insertion in the BRCA1 Exon 14 Associated with Hereditary Breast and Ovarian Cancer
Bouras, A., Léoné, M., Bonadona, V., Lebrun, M., Calender, A., & Boutry-Kryza, N. (2021) · Genes · doi:10.3390/genes12111736 · Cited by 10
“The recommendations of the French Unicancer genetic Group were followed for the interpretation of the results [13].”
Splicing analysis of SLC40A1 missense variations and contribution to hemochromatosis type 4 phenotypes
Tertre, M. L., Ka, C., Raud, L., Berlivet, I., Gourlaouen, I., Richard, G., Uguen, K., Chen, J., Férec, C., Fichou, Y., et al. (2020) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2020.102527 · Cited by 13
A functional assay for the clinical annotation of genetic variants of uncertain significance in Diamond–Blackfan anemia
Aspesi, A., Betti, M., Sculco, M., Actis, C., Olgasi, C., Wlodarski, M., Vlachos, A., Lipton, J., Ramenghi, U., Santoro, C., et al. (2018) · Human Mutation · doi:10.1002/humu.23551 · Cited by 10
Genetic variants of prospectively demonstrated phenocopies in BRCA1/2 kindreds
Dominguez-Valentin, M., Evans, D., Nakken, S., Tubeuf, H., Vodák, D., Ekstrøm, P. O., Nissen, A. M., Morak, M., Holinski-Feder, E., Martins, A., et al. (2018) · Hereditary Cancer in Clinical Practice · doi:10.1186/s13053-018-0086-0 · Cited by 10
First description of a sporadic breast cancer in a woman with BRCA1 germline mutation
Curtit, E., Benhamo, V., Gruel, N., Popova, T., Manié, E., Cottu, P., Mariani, O., Stoppa-Lyonnet, D., Pivot, X., Stern, M., et al. (2015) · OncoTarget · doi:10.18632/oncotarget.5348 · Cited by 10
“DNA was extracted from a blood sample according to standard procedures [31].”
MethodSelf-citation
Consistency of variant interpretations among bioinformaticians and clinical geneticists in hereditary cancer panels
Ağaoğlu, N., Unal, B., Dogan, O. A., Kanev, M. O., Zolfagharian, P., Sag, S. O., Temel, S., & Doğanay, L. (2022) · European Journal of Human Genetics · doi:10.1038/s41431-022-01060-7 · Cited by 9
“9117 G > A, which creates a truncating protein [25, 29] and the BI_1 encoded PVS1 evidence.”
Background
Functional characterization of ABCC8 variants of unknown significance based on bioinformatics predictions, splicing assays and protein analyses: benefits for the accurate diagnosis of congenital hyperinsulinism
Saint-Martin, C., Mière, M. C.-L., Rex, E. A., Soukarieh, O., Arnoux, J., Buratti, J., Bouvet, D., Frebourg, T., Gaildrat, P., Shyng, S., et al. (2021) · Human Mutation · doi:10.1002/humu.24164 · Cited by 9
“…three bioinformatics approaches: (i) the combined MaxEntScan (MES) and SpliceSiteFinder‐like (SSFL) pipeline that is based on the sequential utilization of the aforementioned algorithms (MES/ SSFL) as previously recommended (Houdayer et al., 2012), both si- multaneously accessed via Alamut Visual1.”
MethodSelf-citation
Benchmarking of Amplicon-Based Next-Generation Sequencing Panels Combined with Bioinformatics Solutions for Germline BRCA1 and BRCA2 Alteration Detection.
Vendrell, J., Vilquin, P., Larrieux, M., Goethem, C. V., & Solassol, J. (2018) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2018.06.003 · Cited by 9
“From our perspective, the most problematic concern arose with the Ion AmpliSeq BRCA Panel, which presented a systematic weakness in depth coverage for exons 20 and 23 of BRCA2 .”
Background
Correction: Exonic Splicing Mutations Are More Prevalent than Currently Estimated and Can Be Predicted by Using In Silico Tools
Soukarieh, O., Gaildrat, P., Hamieh, M., Drouet, A., Baert-Desurmont, S., Frebourg, T., Tosi, M., & Martins, A. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005971 · Cited by 9
Self-citation
Investigating the effect of 28 BRCA1 and BRCA2 mutations on their related transcribed mRNA
Quiles, F., Menéndez, M., Tornero, E., del Valle, J., Teulé, À., Palanca, S., Izquierdo, A., Gómez, C., Campos, O., Santamaría, R., et al. (2016) · Breast Cancer Research and Treatment · doi:10.1007/s10549-015-3676-9 · Cited by 9
Pelizaeus-Merzbacher–Like Disease in a Family With Variable Phenotype and a Novel Splicing GJC2 Mutation
Al-Yahyaee, S., Al-Kindi, M., de Jonghe, P., Al-Asmi, A., AlFutaisi, A., Vriendt, E. D., Deconinck, T., & Chand, P. (2013) · Journal of Child Neurology · doi:10.1177/0883073812463610 · Cited by 9
“The AG/GT disruption is systematically associated with deleterious effects except in the presence of strong cryptic sites within the vicinity of the mutation.(20) Using a webbased in silico splicing tool (http://www.”
Method
Mutations at a split codon in the GTPase-encoding domain of OPA1 cause dominant optic atrophy through different molecular mechanisms
Weisschuh, N., Marino, V., Schäferhoff, K., Richter, P., Park, J., Haack, T., & Dell'Orco, D. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab286 · Cited by 8
“For instance, the use of 15% and 5% as cut-off values have been suggested for MaxEntScan and SSF-like, respectively (40).”
Method
Thorough in silico and in vitro cDNA analysis of 21 putative BRCA1 and BRCA2 splice variants and a complex tandem duplication in BRCA2 allowing the identification of activated cryptic splice donor sites in BRCA2 exon 11
Baert, A., Macháčková, E., Coene, I., Cremin, C., Turner, K., Portigal-Todd, C., Asrat, M., Nuk, J., Mindlin, A., Young, S. S., et al. (2018) · Human Mutation · doi:10.1002/humu.23390 · Cited by 8
“Indeed, variants in the highly conserved dinucleotides at the splice site donor/acceptor sites at the intron boundaries, in the conserved adjacent sequences or variants in the branchpoints and exonic splicing enhancers (ESE) might lead to aberrant splicing (Houdayer et al., 2012; Spurdle, Couch, Hogervorst, Radice, &…”
BackgroundInfluential
Parallel DNA/RNA NGS Using an Identical Target Enrichment Panel in the Analysis of Hereditary Cancer Predisposition.
Kleiblová, P., Černá, M., Zemánková, P., Matějková, K., Nehasil, P., Hojný, J., Horackova, K., Janatová, M., Soukupová, J., Stastna, B., et al. (2024) · Folia biologica · doi:10.14712/fb2024070010062 · Cited by 8
Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset
Davidson, A. L., Michailidou, K., Parsons, M. T., Fortuño, C., Bolla, M. K., Wang, Q., Dennis, J., Naven, M., Abubakar, M., Ahearn, T. U., et al. (2024) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2024.07.004 · Cited by 7
Overview of the Genetic Causes of Hereditary Breast and Ovarian Cancer Syndrome in a Large French Patient Cohort
Bouras, A., Guidara, S., Léoné, M., Buisson, A., Martin-Denavit, T., Dussart, S., Lasset, C., Giraud, S., Bonnet-Dupeyron, M., Kherraf, Z., et al. (2023) · Cancers · doi:10.3390/cancers15133420 · Cited by 7
“Interpretation of results was carried out according to the recommendations of the French GGC Unicancer [16].”
Method
Characterising splicing defects of ABCA4 variants within exons 13-50 in patient-derived fibroblasts.
Huang, D., Thompson, J. A., Chen, S., Adams, A., Pitout, I. L., Lima, A., Zhang, D., Jeffery, R. C. H., Attia, M., McLaren, T., et al. (2022) · Experimental Eye Research · doi:10.2139/ssrn.4113528 · Cited by 7
Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID-19
López‐Rodríguez, R., Pozo‐Valero, M. D., Cortón, M., Mínguez, P., Ruiz‐Hornillos, J., Pérez-Tomás, M. E., Barreda‐Sánchez, M., Mancebo, E., Villaverde, C., Núñez‐Moreno, G., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-14035-x · Cited by 11
MLH1 intronic variants mapping to + 5 position of splice donor sites lead to deleterious effects on RNA splicing
Piñero, T. A., Soukarieh, O., Rolain, M., Álvarez, K., López-Köstner, F., Torrezan, G. T., Carraro, D. M., Nascimento, I., Bomfim, T. F., Machado-Lopes, T. M. B., et al. (2020) · Familial Cancer · doi:10.1007/s10689-020-00182-5 · Cited by 8
GFP-Fragment Reassembly Screens for the Functional Characterization of Variants of Uncertain Significance in Protein Interaction Domains of the BRCA1 and BRCA2 Genes
Caleca, L., Colombo, M., Hansen, T. V. O., Lázaro, C., Manoukian, S., Parsons, M., Spurdle, A., & Radice, P. (2019) · Cancers · doi:10.3390/cancers11020151 · Cited by 7
Клинические рекомендации Российской ассоциации эндокринологов по дифференциальной диагностике инциденталом надпочечников
Германович, Б. Д., Афанасьевна, М. Г., Сергеевич, К. Н., Анатольевна, Т. Е., Платонова, Н. М., Эдуардович, В. В., Юрьевна, Ю. М., & Валерьевна, М. Н. (2015) · CyberLeninK (CyberLeninka) · doi:10.14341/serg7768-5615 · Cited by 7
Two founder variants account for over 90% of pathogenic BRCA alleles in the Orkney and Shetland Isles in Scotland
Kerr, S. M., Klarić, L., Muckian, M. D., Cowan, E., Snadden, L., Tzoneva, G., Shuldiner, A. R., Miedzybrodzka, Z., & Wilson, J. F. (2024) · European Journal of Human Genetics · doi:10.1038/s41431-024-01704-w · Cited by 5
“Experimental evidence in vitro supports these bioinformatic predictions [16, 17].”
A respiratory/Hirschsprung phenotype in a three‐generation family associated with a novel pathogenic PHOX2B splice donor mutation
Pace, N., Pace-Bardon, M., & Borg, I. (2020) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.1528 · Cited by 6
“The predictions from both Human Splicing Finder (HSF) and MaxEntScan (MES) are deleterious according to Houdayer's criteria (Houdayer, 2011; Houdayer et al., 2012).”
Method
Diagnostic mRNA splicing assay for variants in BRCA1 and BRCA2 identified two novel pathogenic splicing aberrations
Wangensteen, T., Felde, C. N., Ahmed, D., Mæhle, L., & Ariansen, S. (2019) · Hereditary Cancer in Clinical Practice · doi:10.1186/s13053-019-0113-9 · Cited by 6
In vivo and In vitro methods to identify DNA sequence variants that alter RNA Splicing
Patel, P. N., Gorham, J., Ito, K., & Seidman, C. (2018) · Current Protocols in Human Genetics · doi:10.1002/cphg.60 · Cited by 6
“Software programs exist that predict whether any of these VUS have an effect on splicing; however, the poor speciﬁcity of these tools prevents their reliable application to variant interpretation (Houdayer et al., 2012; Jian, Boerwinkle, & Liu, 2014; Vreeswijk et al., 2009).”
Background
A novel mutation (c.121‑13T>A) in the polypyrimidine tract of the splice acceptor site of intron 2 causes exon 3 skipping in mitochondrial acetoacetyl-CoA thiolase gene.
Aoyama, Y., Sasai, H., Abdelkreem, E., Otsuka, H., Nakama, M., Kumar, S., Aroor, S., Shukla, A., & Fukao, T. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6434 · Cited by 6
“It seems that our knowledge about the splicing process has yet to be optimized (26,30).”
Pros and cons of HaloPlex enrichment in cancer predisposition genetic diagnosis
Collet, A., Tarabeux, J., Girard, E., d'Enghien, C. D., Golmard, L., Deshaies, V., Lermine, A., Laugé, A., Moncoutier, V., Lefol, C., et al. (2015) · AIMS Genetics · doi:10.3934/genet.2015.4.263 · Cited by 6
“Region of interest (ROI) was defined as coding sequences and flanking splice consensus sequences from genes of interest (padding: −20/+10 bp) with 13,266 different amplicons [7].”
MethodSelf-citation
Additional molecular and clinical evidence open the way to definitive IARC classification of the BRCA1 c.5332G > A (p.Asp1778Asn) variant.
Minucci, A., Lalle, M., Leo, R. D., Mazzuccato, G., Scambia, G., Urbani, A., Fagotti, A., Concolino, P., & Capoluongo, E. (2019) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2018.10.004 · Cited by 6
Missense Variants in COL4A1/2 Are Associated with Cerebral Aneurysms: A Case Report and Literature Review
(2024) · doi:10.3390/neurolint16010015 · Cited by 5
“The %variance of MES reflects the difference between the wild-type and mutant MES, expressed as a percentage of wild-type MES [11].”
Background
Functional evaluation of BRCA1/2 variants of unknown significance with homologous recombination assay and integrative in silico prediction model
Guo, Q., Ji, S.-T., Takeuchi, K., Urasaki, W., Suzuki, A., Iwasaki, Y., Saito, H., Xu, Z., Arai, M., Nakamura, S., et al. (2023) · Journal of Human Genetics · doi:10.1038/s10038-023-01194-6 · Cited by 5
“We believe that the present study provides a functional evaluation approach for the advancement of precision medicine.”
Method
Analyzing the effects of BRCA1/2 variants on mRNA splicing by minigene assay
Dong, Z., Wang, Y., Zhang, J., Zhu, F.-W., Liu, Z., Kang, Y., Lin, M., & Shi, H. (2022) · Journal of Human Genetics · doi:10.1038/s10038-022-01077-2 · Cited by 5
“…et al., 2012 [24] BRCA2 c.9502-12 T > G Intron25 No affect No affect Houdayer et al., 2012 [35] BRCA1 c.5406+ 8 T > C Intron22 No affect No affect Houdayer et al., 2012 [35] BRCA2 c.8954-15 T > G Intron22 Ex23_14-nt insertion CTTTCTCCAAACAGa Ex23_14-nt insertion CTTTCTCCAAACAG Menéndez et al.,…”
Background
Identification and in-silico characterization of splice-site variants from a large cardiogenetic national registry
Rayani, K., Davies, B., Cheung, M., Comber, D., Roberts, J. D., Tadros, R., Green, M., Healey, J., Simpson, C., Sanatani, S., et al. (2022) · European Journal of Human Genetics · doi:10.1038/s41431-022-01193-9 · Cited by 5
“Other groups have shown this tool to be highly accurate when analyzing splice donor sites [29] and Jian et al.”
Method
Splicing Analysis of 16 PALB2 ClinVar Variants by Minigene Assays: Identification of Six Likely Pathogenic Variants
Valenzuela-Palomo, A., Sanoguera-Miralles, L., Bueno-Martínez, E., Esteban-Sánchez, A., Llinares-Burguet, I., García-Álvarez, A., Pérez-Segura, P., Gómez-Barrero, S., de la Hoya, M., & Velasco-Sampedro, E. A. (2022) · Cancers · doi:10.3390/cancers14184541 · Cited by 5
“Candidate variants were analyzed under the following criteria [28]: (i) splice site disruption at the ±1,2 (AG/GT) positions and (ii) relevant MES score changes (≥15%) [33,34].”
An intronic mutation c.6430-3C>G in the F8 gene causes splicing efficiency and premature termination in hemophilia A
Xia, Z., Lin, J., Lu, L., Kim, C., Yu, P., & Qi, M. (2018) · Blood Coagulation and Fibrinolysis · doi:10.1097/mbc.0000000000000730 · Cited by 5
High Frequency Actionable Pathogenic Exome Mutations in an Average-Risk CohortPreprint
Rego, S. M., Dagan‐Rosenfeld, O., Zhou, W., Sailani, M. R., Limcaoco, P., Colbert, E., Avina, M., Wheeler, J., Craig, C. M., Salins, D. N., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/151225 · Cited by 5
“Splice site predictors are only slightly more accurate (Vreeswijk et al. 2009; Houdayer et al. 2012).”
Background
AlphaMissense for Identifying Pathogenic Missense Mutations in DNA Damage Repair Genes in Cancer
Yazaki, S., Pei, X., Powell, S. N., Khan, A. J., Setton, J. S., & Riaz, N. (2025) · JCO Precision Oncology · doi:10.1200/po-24-00908 · Cited by 4
Reclassification of Five BRCA1/2 Variants with Unknown Significance Using Complex Functional Study
Bozsik, A., Papp, J., Grolmusz, V. K., Patócs, A., Oláh, E., & Butz, H. (2022) · Cancer Research and Treatment · doi:10.4143/crt.2021.1078 · Cited by 5
Identification and Characterization of an Exonic Duplication in PALB2 in a Man with Synchronous Breast and Prostate Cancer
Bouras, A., Lafaye, C., Léoné, M., Kherraf, Z., Martin-Denavit, T., Fert-Ferrer, S., Calender, A., & Boutry-Kryza, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020667 · Cited by 4
“The recommendations of the French Unicancer genetic Group were followed for the interpretation of the results [27].”
Method
Aktualisierte Kriterien des Deutschen Konsortiums Familiärer Brust- und Eierstockkrebs zur Klassifizierung von Keimbahn-Sequenzvarianten in Risikogenen für familiären Brust- und Eierstockkrebs
Hauke, J., Wappenschmidt, B., Faust, U., Niederacher, D., Wiesmüller, L., Schmidt, G., Groß, E., Meindl, A., Gehrig, A., Sutter, C., et al. (2021) · Senologie - Zeitschrift für Mammadiagnostik und -therapie · doi:10.1055/a-1342-5231 · Cited by 4
A synonymous germline variant PALB2 c.18G>T (p.Gly6= ) disrupts normal splicing in a family with pancreatic and breast cancers
Yang, C.-Y., Ceyhan-Birsoy, O., Mandelker, D., Jairam, S., Catchings, A., O'Reilly, E., Walsh, M., & Zhang, L.-Y. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-4980-y · Cited by 4
“Despite the variability in their predictions, they have been reported to have high sensitivity to predict splice sites, although their specificity may be low [32, 33].”
A novel splice site mutation of the PRKAR1A gene, C.440+5 G>C, in a Chinese family with Carney complex
Fu, J., Lai, F., Chen, Y., Wan, X., Wei, G., Li, Y.-H., Xiao, H.-M., & Cao, X. (2018) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0817-5 · Cited by 4
A Novel Germline Mutation in BRCA1 Causes Exon 20 Skipping in a Korean Family with a History of Breast Cancer
Yoon, K., Kong, S.-Y., Lee, E. J., Cho, J. N., Chang, S., & Lee, E. S. (2017) · Journal of Breast Cancer · doi:10.4048/jbc.2017.20.3.310 · Cited by 4
“Splicing variants in exons 19−21 of the BRCA1 gene that cause exon skipping or intron retention due to aberrant splicing have been reported in patients with breast cancers [10,14].”
Background
New Molecular Diagnosis Approaches — From the Identification of Mutations to their Characterization
Bergougnoux, A., Taulan-Cadars, M., Claustres, M., & Raynal, C. (2015) · InTech eBooks · doi:10.5772/60679 · Cited by 4
The contribution of non-canonical splicing mutations to severe dominant developmental disordersPreprint
Lord, J., Gallone, G., Short, P. J., McRae, J. F., Ironfield, H., Elizabeth, H., Wynn, Gerety, S., He, L., Kerr, B., et al. (2018) · bioRxiv · doi:10.1101/256636 · Cited by 3
A prioritization framework for BRCA1/2 variants of uncertain significance identified by comprehensive genomic profiling
Nakahara, H., Niitsu, H., Toshida, A., Goto, K., Yamauchi, M., Saipova, K., Hayes, C. N., Hinata, N., Oka, S., & Hinoi, T. (2026) · European Journal of Human Genetics · doi:10.1038/s41431-026-02058-1 · Cited by 3
“Compared with Bose ’ s study, which suggested PS3_Moderate evidence, our work further contributed PS1 (Splicing)_Moderate based on similarity to other splice donor variants such as BRCA2 :c.67+1 A > G and BRCA2 :c.67+2 T > C (See also Supplementary Table S4) [32, 33].”
Evaluation of pathogenicity of WT1 intron variants by in vitro splicing analysis
Inoue, S., Kondo, A., Inoki, Y., Ichikawa, Y., Tanaka, Y., Ueda, C., Kitakado, H., Suzuki, R., Okada, E., Sakakibara, N., et al. (2024) · Clinical and Experimental Nephrology · doi:10.1007/s10157-024-02510-w · Cited by 3
The TSC2 c.2742+5G>A variant causes variable splicing changes and clinical manifestations in a family with tuberous sclerosis complex
Fan, K., Guo, Y., Song, Z., Yuan, L.-M., Zheng, W., Hu, X., Gong, L., & Deng, H. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1091323 · Cited by 3
“In addition to determining the loss of wild-type splice sites, it is also necessary to find cryptic sites that may be used by the splicing mechanism because new splice sites close to the destroyed wild-type site possibly only lead to the deletion or insertion of a few amino acids (Houdayer et al., 2012).”
Background
Identification of Spliceogenic Variants beyond Canonical GT-AG Splice Sites in Hereditary Cancer Genes
Dragos, V., Strojnik, K., Klančar, G., Škerl, P., Stegel, V., Blatnik, A., Banjac, M., Krajc, M., & Novaković, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137446 · Cited by 3
“It is estimated that 15–25% of DNA variants in hereditary cancer genes cause mis-splicing [5].”
BackgroundInfluential
Characterization of Synonymous BRCA1:c.132C>T as a Pathogenic Variant
Li, J., Wang, P.-L., Zhang, C., Han, S., Xiao, H., Liu, Z., Wang, X., Liu, W.-L., Wei, B., Ma, J., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.812656 · Cited by 3
The Interpretation of Sequence Variants in Myeloid Neoplasms
Hanbazazh, M., Harada, S., Reddy, V., Mackinnon, A. C., Harbi, D., & Morlote, D. M. (2021) · American Journal of Clinical Pathology · doi:10.1093/ajcp/aqab039 · Cited by 4
Translating RNA Splicing Analysis into Diagnosis and Therapy
Douglas, A. G. L., & Baralle, D. (2021) · OBM Genetics · doi:10.21926/obm.genet.2101125 · Cited by 3
“understanding of how such complexes are regulated, it is not surprising that these predictions often turn out to be wrong [8-10].”
Background
Protein haploinsufficiency drivers identify MYBPC3 mutations that cause hypertrophic cardiomyopathy
Suay-Corredera, C., Pricolo, M. R., Herrero-Galan, E., Velazquez-Carreras, D., Sanchez-Ortiz, D., Garcia-Giustiniani, D., Delgado, J., Galano-Frutos, J. J., Garcia-Cebollada, H., Vilches, S., et al. (2020) · medRxiv · doi:10.1101/2020.05.04.20087726 · Cited by 3
The SeqSplice multiplexed minigene splicing assay for characterization and quantitation of variant-induced BRCA1 and BRCA2 splice isoforms
Canson, D., Parsons, M., Moir-Meyer, G., Dumenil, T., Montalban, G., Lin, E., McVeigh, T. P., Davidson, A. L., Bouckaert, S. M., Trau, M., et al. (2025) · Genome Research · doi:10.1101/gr.279557.124 · Cited by 2
“…et al. 2014; Li et al. 2022), BRCA1 c.190T>G ( Δ 5q22) (Yang et al. 2003), BRCA1 c.4097-2A>G ( ▾ 12p1) (Leman et al. 2018), BRCA2 c.572A>G ( Δ 7q60) (Gaildrat et al. 2012; Fraile-Bethencourt et al. 2019), and BRCA2 c.681+4A>G ( ▾ 8q4) (Houdayer et al. 2012; Fraile-Bethencourt et al. 2019).”
Molecular analysis of BRCA1 and BRCA2 genes in La Rioja (Spain): five new variants
Saez, R. S., Zorrilla, M., Sánchez, R., Cebollero, A., Manrique, I., Martín, A., de Ávila, L. G., Lacalle-Emborujo, A., Martin-Rodriguez, S., Bernardo-González, I., et al. (2024) · Hereditary Cancer in Clinical Practice · doi:10.1186/s13053-024-00296-2 · Cited by 2
“The c.632–3 C > G variant in BRCA2 was classified as pathogenic by Houdayer et al. [40].”
Background
Unpredicted Aberrant Splicing Products Identified in Postmortem Sudden Cardiac Death Samples
Coll, M., Fernández-Falgueras, A., Iglesias, A., del Olmo, B., Nogué-Navarro, L., Simon, A. R., Serra, A. P., Puigmulé, M., López, L., Picó, F., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012640 · Cited by 2
Pathogenicity of missense variants affecting the collagen IV α5 carboxy non-collagenous domain in X-linked Alport syndrome
Gibson, J., Sadeghi-Alavijeh, O., Gale, D., Rothe, H., Savige, J., Ambrose, J., Arumugam, P., Baple, E., Bleda, M., Boardman-Pretty, F., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-14928-x · Cited by 2
New Approach for Detection of Normal Alternative Splicing Events and Aberrant Spliceogenic Transcripts with Long-Range PCR and Deep RNA Sequencing
Dragos, V., Stegel, V., Blatnik, A., Klančar, G., Krajc, M., & Novaković, S. (2021) · Biology · doi:10.3390/biology10080706 · Cited by 2
“Crucial for any RNAseq experiment is its ability to accurately detect splicing impairment [24].”
Background
Empirical prediction of variant-associated cryptic-donors with 87% sensitivity and 95% specificity
Dawes, R., Joshi, H., & Cooper, S. (2021) · bioRxiv · doi:10.1101/2021.07.18.452855 · Cited by 2
Whole Sequencing of Most Prevalent Dilated Cardiomyopathy-Causing Genes as a Molecular Strategy to Improve Molecular Diagnosis Efficiency?
Januel, L., Chanavat, V., Rollat-Farnier, P., Bardel, C., Nony, S., Millat, G., & Janin, A. (2021) · DNA and Cell Biology · doi:10.1089/dna.2020.6305 · Cited by 2
“Cutoff values used were based on those previously determined by Houdayer et al. (2012).”

Authors: Houdayer, C., Caux-Moncoutier, V., Krieger, S., Barrois, M., Bonnet, F., Bourdon, V., Bronner, M., Buisson, M., Coulet, F., Gaildrat, P., Lefol, C., Léone, M., Mazoyer, S., Muller, D., Remenieras, A., Révillion, F., Rouleau, E., Sokolowska, J., Vert, J.-P., Lidereau, R., Soubrier, F., Sobol, H., Sevenet, N., Bressac-de Paillerets, B., Hardouin, A., Tosi, M., Sinilnikova, O. M., & Stoppa-Lyonnet, D.
Affiliations: Sorbonne Paris Cité (FR)
Centre François Baclesse (FR)
Institut Gustave Roussy (FR)
Inserm (FR)
Institut Paoli-Calmettes (FR)
Centre Hospitalier Régional et Universitaire de Nancy (FR)
Lyon 1 Université (FR)
Assistance Publique – Hôpitaux de Paris (FR)
Hôpital René Huguenin (FR)
Institut Strauss (FR)
Corresponding author: Houdayer, Claude
ORCID: Houdayer, Claude
Krieger, Sophie
Bourdon, Violaine
Bronner, Myriam
Coulet, Florence
Gaildrat, Pascaline
Mazoyer, Sylvie
Vert, Jean-Philippe
Soubrier, Florent
Sobol, Hagay
Venue: Human Mutation
Publisher: Hindawi Limited
Published: 2012-05-11
Volume: 33
Issue: 8
Pages: 1228-1238
ISSN: 1059-7794 (ISSN-L)
DOI: 10.1002/humu.22101
OpenAlex: W1975196485
Cited by: 239
References: 0
Citations by year: 2026: 3 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 25 · 2021: 27 · 2020: 22 · 2019: 23 · 2018: 27 · 2017: 23 · 2016: 14 · 2015: 22 · 2014: 11 · 2013: 17 · 2012: 3
FWCI: 10.21
Type: journal article
Language: en
Open access: closed
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1208 d)
Locations: Human Mutation (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords: BRCA1, BRCA2, variants of uncertain significance, splicing, splice site prediction, in silico tools, transcript analysis, variant interpretation, molecular diagnosis
MeSH terms: Exons, Female, Humans, RNA Splicing, BRCA1 Protein, BRCA2 Protein, Pathology, Molecular

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Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants

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