Not-so-incidental findings: the ACMG recommendations on the reporting of incidental findings in clinical whole genome and whole exome sequencing.

Introduction The issue of incidental findings in genomics research has been contentious, particularly in whole genome sequencing (WGS) and whole exome sequencing (WES). An incidental or secondary finding has generally been defined as ‘a finding concerning an individual research participant that has potential health or reproductive importance and is discovered in the course of conduct – but is beyond the aims of the study.’ [1]. However, as WGS and WES increasingly enter the clinical realm, these concerns are extended to individually relevant findings that are unrelated to the clinical purpose of sequencing. In May 2012, the American College of Medical Genetics and Genomics (ACMG) released a policy statement on Points to Consider in the Clinical Application of Genomic Sequencing in which they cautioned that ‘when interpreting secondary findings, or results that are generated in the course of screening asymptomatic individuals, it is critical that the standards for what is reportable be high to avoid burdening the health care system and consumers with what could be very large numbers of false positive results’ [2]. As a result, ACMG convened a working group to offer recommendations on handling incidental findings in clinical sequencing. The Working Group on Incidental Findings in Clinical Exome and Genome Sequencing of the ACMG (‘the Working Group’) published its Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing (‘the recommendations’) in March 2013 [3]. On the one hand, the recommendations take seriously the need to focus incidental findings on only those findings with clear clinical utility and actionable results. They provide a stringently curated list of specific variants that they believe rise to the level of clinical obligation to report. On the other hand, the zeal with which these variants were selected apparently encouraged the Working Group towards recommendations that depart significantly from existing practice and policy. First, they suggest that rather than reporting findings that are incidental to the purpose of the clinical sequencing as ordered, clinical sequencing laboratories have an obligation to seek out actively the variants as listed in the recommendations and include