ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing

• Type of Material: Article
• Authors: Robert Green, Emory University; Jonathan S Berg, University of North Carolina; Wayne W Grody, University of California Los Angeles; Sarah S Kalia, Brigham & Womens Hospital; Bruce R Korf, University of Alabama Birmingham; Christa Martin, Emory University; Amy L McGuire, Baylor College of Medicine; Robert L Nussbaum, University of California San Francisco; Julianne M O'Daniel, University of North Carolina; Kelly E Ormond, Stanford University
• Language: English
• Date: 2013-07-01
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © American College of Medical Genetics and Genomics.
• Final Published Version (URL): http://dx.doi.org/10.1038/gim.2013.73
• Title of Journal or Parent Work: Genetics in Medicine
• Volume: 15
• Issue: 7
• Start Page: 565
• End Page: 574
• Grant/Funding Information: Research funding from the following sources supported efforts by members of this Working Group: HG006500 (Green, Rehm, Maguire); HG005092, HG003178, HG00603, HG006615, HG003170, GM007748, AG027841, CA154517 (Green); HG003389 (Ormond); HG006382 (Williams); HG006500, HG006485, HG006612 (Maguire); ES017793, DK087728, Michael J. Fox Foundation, National Parkinson Disease Foundation and DOD W81XWH-12-1-0569 (Nussbaum); HG004488, RR025747, RR025746, RR025745, HG006487, UNC Cancer Research Fund, UNC Bryson Philanthropic Fund, and the UNC Center for Genomics and Society (Berg).; Dr. Biesecker is supported by the Intramural Research Program of the National Human Genome Research Institute
• Keywords: incidental findings; personalized medicine; whole genome; FUTURE; genome; Genetics & Heredity; genomic medicine; Life Sciences & Biomedicine; sequencing; RETURN; secondary findings; whole exome; Science & Technology; MEDICINE; GENETICS
• Research Categories: Biology, Genetics; Health Sciences, Medicine and Surgery

Abstract

In clinical exome and genome sequencing, there is a potential for the recognition and reporting of incidental or secondary findings unrelated to the indication for ordering the sequencing but of medical value for patient care. The American College of Medical Genetics and Genomics (ACMG) recently published a policy statement on clinical sequencing that emphasized the importance of alerting the patient to the possibility of such results in pretest patient discussions, clinical testing, and reporting of results. The ACMG appointed a Working Group on Incidental Findings in Clinical Exome and Genome Sequencing to make recommendations about responsible management of incidental findings when patients undergo exome or genome sequencing. This Working Group conducted a year-long consensus process, including an open forum at the 2012 Annual Meeting and review by outside experts, and produced recommendations that have been approved by the ACMG Board. Specific and detailed recommendations, and the background and rationale for these recommendations, are described herein. The ACMG recommends that laboratories performing clinical sequencing seek and report mutations of the specified classes or types in the genes listed here. This evaluation and reporting should be performed for all clinical germline (constitutional) exome and genome sequencing, including the "normal" of tumor-normal subtractive analyses in all subjects, irrespective of age but excluding fetal samples. We recognize that there are insufficient data on penetrance and clinical utility to fully support these recommendations, and we encourage the creation of an ongoing process for updating these recommendations at least annually as further data are collected.