American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants
Open accessAbstract
Genomic microarrays used to assess DNA copy number are now recommended as first-tier tests for the postnatal evaluation of individuals with intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies. Application of this technology has resulted in the discovery of widespread copy number variation in the human genome, both polymorphic variation in healthy individuals and novel pathogenic copy number imbalances. To assist clinical laboratories in the evaluation of copy number variants and to promote consistency in interpretation and reporting of genomic microarray results, the American College of Medical Genetics has developed the following professional guidelines for the interpretation and reporting of copy number variation. These guidelines apply primarily to evaluation of constitutional copy number variants detected in the postnatal setting.
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The terms recommended in this report differ somewhat from the current recommendations for classifying copy number variants detected by cytogenetic microarray.
“the terms recommended here differ somewhat from the current recommendations for classifying copy number variants (CNVs) detected by cytogenetic microarray. 6”
Variants with uncertain clinical significance are subcategorised into likely pathogenic, likely benign, and no subclassification.
“Variants with uncertain clinical significance are subcategorised in likely pathogenic, likely benign and no subclassification.”
From Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice (2019) · cites this paper as [45]
The American College of Medical Genetics guidelines recommend three categories of clinical significance: pathogenic, uncertain clinical significance, and benign.
“The guidelines of the American College of Medical Genetics45 46 recommend three categories of clinical significance including pathogenic, uncertain clinical significance and benign.”
From Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice (2019) · cites this paper as [45]
The clinical relevance of CNVs was interpreted according to the American College of Medical Genetics guidelines irrespective of the subjects' affected status.
“The clinical relevance of CNVs was interpreted according to the American College of Medical Genetics guidelines32 irrespective of the subjects’ affected status, and CNVs were classified as pathogenic, uncertain, or benign.”
From Convergence of genes and cellular pathways dysregulated in autism spectrum disorders (2014) · cites this paper as [32]
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- Authors
- Kearney, H. M., Thorland, E. C., Brown, K. K., Quintero-Rivera, F., & South, S. T.
- Affiliations
- Mission Health (US)
- Mayo Clinic (US)
- Brigham and Women's Hospital (US)
- University of Utah (US)
- ORCID
- Kearney, Hutton M.
- Venue
- Genetics in Medicine
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 13
- Issue
- 7
- Pages
- 680-685
- ISSN
- 1098-3600 (ISSN-L)
- OpenAlex
- W1991633140
- Cited by
- 929
- References
- 29
- Citations by year
- 2026: 23 · 2025: 32 · 2024: 52 · 2023: 51 · 2022: 99 · 2021: 98 · 2020: 101 · 2019: 112 · 2018: 92 · 2017: 59 · 2016: 67 · 2015: 37 · 2014: 32 · 2013: 40 · 2012: 27
- FWCI
- 21.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Genetics in Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
- Keywords
- genomic microarrays, intellectual disability, autism spectrum disorder, multiple congenital anomalies, professional guidelines
- MeSH terms
- Abnormalities, Multiple, Autistic Disorder, Child, Developmental Disabilities, Genetics, Medical, Humans, Intellectual Disability, Genetic Variation, Genome, Human, Gene Dosage, Clinical Laboratory Techniques, Microarray Analysis
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