The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index.
Recommendations for clinical interpretation of variants found in non-coding regions of the genome
Open accessAbstract
Background: The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease is, however, increasingly being demonstrated, and the use of whole genome sequencing in clinical diagnostic settings is rising across a large range of genetic disorders. Despite this, there is no existing guidance on how current guidelines designed primarily for variants in protein-coding regions should be adapted for variants identified in other genomic contexts. Methods: We convened a panel of nine clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. This panel discussed and refined an initial draft of the guidelines which were then extensively tested and reviewed by external groups. Results: We discuss considerations specifically for variants in non-coding regions of the genome. We outline how to define candidate regulatory elements, highlight examples of mechanisms through which non-coding region variants can lead to penetrant monogenic disease, and outline how existing guidelines can be adapted for the interpretation of these variants. Conclusions: These recommendations aim to increase the number and range of non-coding region variants that can be clinically interpreted, which, together with a compatible phenotype, can lead to new diagnoses and catalyse the discovery of novel disease mechanisms.
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Cites
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Cited by
Schubach, M., Maass, T., Nazaretyan, L., Röner, S., & Kircher, M. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkad989 · Cited by 455
The performance of genome sequencing as a first-tier test for neurodevelopmental disorders
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The utility of ultra-deep RNA sequencing in Mendelian disorder diagnostics
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Metadata
- Authors
- Ellingford, J. M., Ahn, J. W., Bagnall, R. D., Baralle, D., Barton, S., Campbell, C., Downes, K., Ellard, S., Duff-Farrier, C., FitzPatrick, D. R., Greally, J. M., Ingles, J., Krishnan, N., Lord, J., Martin, H. C., Newman, W. G., O’Donnell-Luria, A., Ramsden, S. C., Rehm, H. L., Richardson, E., Singer-Berk, M., Taylor, J. C., Williams, M., Wood, J. C., Wright, C. F., Harrison, S. M., & Whiffin, N.
- Venue
- Genome Medicine
- Published
- 2022-07-19
- Volume
- 14
- Issue
- 1
- Pages
- 73-73
- ISSN
- 1756-994X (ISSN-L)
- OpenAlex
- W4285796131
- Cited by
- 259
- References
- 83
- FWCI
- 28.81
- Type
- journal article
- Language
- en
- Open access
- gold
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- Ellingford, J. M., Ahn, J. W., Bagnall, R. D., Baralle, D., Barton, S., Campbell, C., Downes, K., Ellard, S., Duff-Farrier, C., FitzPatrick, D. R., Greally, J. M., Ingles, J., Krishnan, N., Lord, J., Martin, H. C., Newman, W. G., O’Donnell-Luria, A., Ramsden, S. C., Rehm, H. L., . . . Whiffin, N. (2022). Recommendations for clinical interpretation of variants found in non-coding regions of the genome. Genome Medicine. https://doi.org/10.1186/s13073-022-01073-3
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