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

Genetics in Medicine

(2013)

15,

565–574

doi:10.1038/gim.2013.73

Received: 11 April 2013
Accepted: 11 April 2013
Published online: 20 June 2013

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.
Genet Med 2013:15(7):565–574

Keywords:

genome; genomic medicine; incidental findings; personalized medicine; secondary findings; sequencing; whole exome; whole genome

Exome and genome sequencing (collectively referred to in this report as clinical sequencing) are rapidly being integrated into the practice of medicine.^1,2 The falling price of sequencing, coupled with advanced bioinformatics capabilities, is creating opportunities to use sequencing in multiple medical situations, including the molecular characterization of rare diseases, the individualization of treatment (particularly in cancer), pharmacogenomics, preconception/prenatal screening, and population screening for disease risk.^3,4 In all of these applications, there is a potential for the recognition and reporting of incidental (or secondary) findings, which are results that are not related to the indication for ordering the sequencing but that may nonetheless be of medical value or utility to the ordering physician and the patient. Considerable literature discusses the utility and ethics of reporting incidental findings discovered in the course of research,^5,6,7,8,9 but relatively little has been written about doing so in the clinical context.^{10,11,12,13,14} Last year, the American College of Medical Genetics and Genomics (ACMG) published a policy statement related to clinical sequencing¹⁵ that emphasized the importance of secondary or incidental results in pretest patient discussions, clinical testing, and reporting of results. Here, we provide the recommendations of the ACMG Working Group on Incidental Findings in Clinical Exome and Genome Sequencing (hereafter referred to as the Working Group). These recommendations have been approved by the Board of the ACMG.