Next-generation sequencing for constitutional variants in the clinical laboratory, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Catherine Rehder; Lora J H Bean; David Bick; Elizabeth Chao; Wendy Chung; Soma Das; Julianne O'Daniel; Heidi Rehm; Vandana Shashi; Lisa M Vincent; ACMG Laboratory Quality Assurance Committee

doi:10.1038/s41436-021-01139-4

Next-generation sequencing for constitutional variants in the clinical laboratory, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Genet Med. 2021 Aug;23(8):1399-1415. doi: 10.1038/s41436-021-01139-4. Epub 2021 Apr 29.

Authors

Affiliations

¹ Department of Pathology, Duke University, Durham, NC, USA.
² Department of Human Genetics, Emory University, Atlanta, GA, USA.
³ HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
⁴ Division of Genetics and Genomics, Department of Pediatrics, University of California, Irvine, CA, USA.
⁵ Departments of Pediatrics and Medicine, Columbia University, New York, NY, USA.
⁶ Department of Human Genetics, University of Chicago, Chicago, IL, USA.
⁷ Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
⁸ Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁹ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Department of Pediatrics, Duke University, Durham, NC, USA.
¹¹ Division of Pathology & Laboratory Medicine, Children's National Health System, Washington, DC, USA.
¹² Departments of Pathology and Pediatrics, George Washington University, Washington, DC, USA.

PMID: 33927380
DOI: 10.1038/s41436-021-01139-4

Abstract

Next-generation sequencing (NGS) technologies are now established in clinical laboratories as a primary testing modality in genomic medicine. These technologies have reduced the cost of large-scale sequencing by several orders of magnitude. It is now cost-effective to analyze an individual with disease-targeted gene panels, exome sequencing, or genome sequencing to assist in the diagnosis of a wide array of clinical scenarios. While clinical validation and use of NGS in many settings is established, there are continuing challenges as technologies and the associated informatics evolve. To assist clinical laboratories with the validation of NGS methods and platforms, the ongoing monitoring of NGS testing to ensure quality results, and the interpretation and reporting of variants found using these technologies, the American College of Medical Genetics and Genomics (ACMG) has developed the following technical standards.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genetic Testing
Genetics, Medical*
Genomics
High-Throughput Nucleotide Sequencing
Humans
Laboratories*
United States