Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Feb;22(2):245-257.
doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.

Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)

Erin Rooney Riggs  1 , Erica F Andersen  2   3 , Athena M Cherry  4 , Sibel Kantarci  5 , Hutton Kearney  6 , Ankita Patel  7 , Gordana Raca  8 , Deborah I Ritter  9 , Sarah T South  10 , Erik C Thorland  6 , Daniel Pineda-Alvarez  11 , Swaroop Aradhya  4   11 , Christa Lese Martin  12
Affiliations

Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)

Erin Rooney Riggs et al. Genet Med. 2020 Feb.

Erratum in

Abstract

Purpose: Copy-number analysis to detect disease-causing losses and gains across the genome is recommended for the evaluation of individuals with neurodevelopmental disorders and/or multiple congenital anomalies, as well as for fetuses with ultrasound abnormalities. In the decade that this analysis has been in widespread clinical use, tremendous strides have been made in understanding the effects of copy-number variants (CNVs) in both affected individuals and the general population. However, continued broad implementation of array and next-generation sequencing-based technologies will expand the types of CNVs encountered in the clinical setting, as well as our understanding of their impact on human health.

Methods: To assist clinical laboratories in the classification and reporting of CNVs, irrespective of the technology used to identify them, the American College of Medical Genetics and Genomics has developed the following professional standards in collaboration with the National Institutes of Health (NIH)-funded Clinical Genome Resource (ClinGen) project.

Results: This update introduces a quantitative, evidence-based scoring framework; encourages the implementation of the five-tier classification system widely used in sequence variant classification; and recommends "uncoupling" the evidence-based classification of a variant from its potential implications for a particular individual.

Conclusion: These professional standards will guide the evaluation of constitutional CNVs and encourage consistency and transparency across clinical laboratories.

Keywords: CNV; classification; copy-number variant; interpretation; scoring metric.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Notification Page

Erin Rooney Riggs has no conflicts to disclose.

Erica F. Andersen is the director of a fee-for-service testing laboratory performing tests mentioned in this technical standard.

Athena M. Cherry is the director of a fee-for-service testing laboratory performing tests mentioned in this technical standard.

Sibel Kantarci is the director of a fee-for-service testing laboratory performing tests mentioned in this technical standard.

Hutton Kearney is the director of a fee-for-service testing laboratory performing tests mentioned in this technical standard.

Ankita Patel has no conflicts to disclose.

Gordana Raca is the director of a fee-for-service testing laboratory performing tests mentioned in this technical standard.

Deborah I. Ritter has no conflicts to disclose.

Sarah T. South is the director of a fee-for-service testing laboratory performing tests mentioned in this technical standard.

Erik C. Thorland is the director of a fee-for-service testing laboratory performing tests mentioned in this technical standard.

Daniel Pineda-Alvaraz is the director of a fee-for-service testing laboratory performing tests mentioned in this technical standard.

Swaroop Aradhya is the director of a fee-for-service testing laboratory performing tests mentioned in this technical standard.

Christa Lese Martin has no conflicts to disclose.

Comment in

References

    1. Manning M, Hudgins L, Professional Practice and Guidelines Committee. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med. 2010;12(11):742–745. doi: 10.1097/GIM.0b013e3181f8baad [doi]. - DOI - PMC - PubMed
    1. Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86(5):749–764. doi: 10.1016/j.ajhg.2010.04.006 [doi]. - DOI - PMC - PubMed
    1. American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 2013;122(6):1374–1377. doi: 10.1097/01.AOG.0000438962.16108.d1 [doi]. - DOI - PubMed
    1. Brothman AR, Dolan MM, Goodman BK, et al. College of American Pathologists/American College of Medical Genetics proficiency testing for constitutional cytogenomic microarray analysis. Genet Med. 2011;13(9):765–769. doi: 10.1097/GIM.0b013e31821d3165 [doi]. - DOI - PubMed
    1. Tsuchiya KD, Shaffer LG, Aradhya S, et al. Variability in interpreting and reporting copy number changes detected by array-based technology in clinical laboratories. Genet Med. 2009;11(12):866–873. doi: 10.1097/GIM.0b013e3181c0c3b0 [doi]. - DOI - PubMed

Publication types