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Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American College of Medical Genetics and Genomics (ACMG)

2021; Elsevier BV; Volume: 23; Issue: 8 Linguagem: Inglês

10.1038/s41436-021-01171-4

1530-0366

David T. Miller, Kristy Lee, Allan Gordon, Laura M. Amendola, Kathy Adelman, Sherri J. Bale, Wendy K. Chung, Michael H. Gollob, Steven M. Harrison, Gail E. Herman, Ray E. Hershberger, Teri E. Klein, Kent D. McKelvey, C. Sue Richards, Christopher N. Vlangos, Douglas R. Stewart, Michael S. Watson, Christa Lese Martin,

Cancer Genomics and Diagnostics

Guidance from the original American College of Medical Genetics and Genomics (ACMG) Policy Statement on incidental findings in 2013 established that clinical laboratories performing exome or genome sequencing (ES/GS) should report known pathogenic (KP) or expected pathogenic (EP) variants in a defined set of genes considered medically actionable, even when unrelated to the primary medical reason for testing. 1. Green R.C. et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. 1:CAS:528:DC%2BC3sXhtVKku73K 23788249 3727274 10.1038/gim.2013.73Genet. Med. 2013; 15: 565-574 Google Scholar Subsequently, the ACMG updated the terminology used to describe these types of findings to align with nomenclature recommendations from the Presidential Commission on Bioethical Issues that defined “secondary findings” (SF) as variants that are actively sought in genes that are part of a defined list, as opposed to genomic variants found incidentally or accidentally. 2. Kalia S.S. et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. 27854360 10.1038/gim.2016.190Genet. Med. 2017; 19: 249-255 Google Scholar In a survey of ACMG members, more than 90% of respondents supported a minimum gene list of SFs that would be updated and refined over time. 3. Scheuner M.T. et al. Reporting genomic secondary findings: ACMG members weigh in. 25394173 10.1038/gim.2014.165Genet. Med. 2015; 17: 27-35 Google Scholar Recognizing this need, the ACMG Board of Directors (BOD) created the ACMG Secondary Findings Maintenance Working Group (SFWG) in 2014 to define and implement a process for updating the SF list. Shortly thereafter, we established a mechanism for ACMG members to submit nominations to add or remove genes from the list through a nomination form found on the ACMG website. 4. ACMG. Secondary findings nomination form. https://www.acmg.net/PDFLibrary/Secondary-Findings-Panel-Nomination-Form.pdf (2021). Google Scholar The 2017 update added four new genes, removed one gene, and rejected one nominated gene from inclusion in the list. Adoption of clinical ES/GS since then has expanded even further. 2. Kalia S.S. et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. 27854360 10.1038/gim.2016.190Genet. Med. 2017; 19: 249-255 Google Scholar The ACMG SFWG and the BOD agree that timely updates to the SF list are increasingly important, which has led to the decision to separate the ACMG SFWG policy update discussed here from the updated ACMG SF gene list. The SFWG will update this general policy statement as needed, but on a less frequent basis, generally every 3–4 years, and the gene list will be updated on an annual basis, with a goal of publishing the updated list each year in January.