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, Erica F. Andersen, Athena M. Cherry, Sibel Kantarci, Hutton Kearney, Ankita Patel, Gordana Raca, Deborah I. Ritter, Sarah T. South, Erik C. Thorland, Daniel Pineda-Alvarez, Swaroop Aradhya, Christa Lese Martin, behalf of the ACMG on behalf of the ACMG

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Purpose: Copy-number analysis to detect disease-causing losses and gainsacross the genome is recommended for the evaluation of individuals withneurodevelopmental disorders and/or multiple congenital anomalies, as well asfor fetuses with ultrasound abnormalities. In the decade that this analysis hasbeen in widespread clinical use, tremendous strides have been made inunderstanding the effects of copy-number variants (CNVs) in both affectedindividuals and the general population. However, continued broad implementationof array and next-generation sequencing–based technologies will expand the typesof CNVs encountered in the clinical setting, as well as our understanding oftheir impact on human health. Methods: To assist clinical laboratories in the classification and reportingof CNVs, irrespective of the technology used to identify them, the AmericanCollege of Medical Genetics and Genomics has developed the followingprofessional standards in collaboration with the National Institutes of Health(NIH)–funded Clinical Genome Resource (ClinGen) project. Results: This update introduces a quantitative, evidence-based scoringframework; encourages the implementation of the five-tier classification systemwidely used in sequence variant classification; and recommends “uncoupling” theevidence-based classification of a variant from its potential implications for aparticular individual. Conclusion: These professional standards will guide the evaluation ofconstitutional CNVs and encourage consistency and transparency across clinicallaboratories.

Original languageEnglish (US)
Pages (from-to)245-257
Number of pages13
JournalGenetics in Medicine
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2020

Keywords

  • CNV
  • classification
  • copy-number variant
  • interpretation
  • scoring metric

ASJC Scopus subject areas

  • Genetics(clinical)

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    Riggs, E. R., Andersen, E. F., Cherry, A. M., Kantarci, S., Kearney, H., Patel, A., Raca, G., Ritter, D. I., South, S. T., Thorland, E. C., Pineda-Alvarez, D., Aradhya, S., Martin, C. L., & on behalf of the ACMG, B. O. T. ACMG. (2020). 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). Genetics in Medicine, 22(2), 245-257. https://doi.org/10.1038/s41436-019-0686-8