Skip to main content
Premium Trial:

Request an Annual Quote

Panel Debates ACMG Incidental Findings Recommendations at Annual Meeting

NASHVILLE, Tenn. (GenomeWeb News) – A panel discussion at the American College of Genetics and Genomics annual meeting here yesterday highlighted the debate that continues to swirl around the recommendations that the ACMG issued last year for dealing with incidental findings in clinically sequenced exomes and genomes.

Participants in the panel included Christine Eng from Baylor College of Medicine's Medical Genetics Laboratories; University of North Carolina clinical geneticist James Evans; Wylie Burke, a bioethicist with the University of Washington; the University of California at San Francisco's Robert Nussbaum; and University of Minnesota law, medicine, and public policy researcher Susan Wolf.

Much of the discussion centered on whether patients should have the choice to opt out of receiving incidental findings related to one or all of the so-called "ACMG 56" — a set of genes in which certain mutations have been deemed to increase the risk of one or more diseases.

ACMG issued a set of recommendations at its annual meeting in Phoenix last year. Those guidelines were subsequently published in the journal Genetics in Medicine. The recommendations originally urged reporting on clinically relevant alterations in 57 genes that have been associated with 24 medical conditions. The set has since been whittled down to 56 based on the strength of evidence for disease risk available.

"We recommend that laboratories performing clinical sequencing seek and report mutations of the specified classes or types of genes listed here," corresponding authors Robert Green of Brigham and Women's Hospital, and the National Human Genome Research Institute's Leslie Biesecker, and colleagues wrote.

"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 clinical utility to fully support these recommendations," they added, "and we encourage the creation of an ongoing process for updating these recommendations at least annually as further data are collected."

At yesterday's panel discussion, Eng noted that the Baylor team reported 95 incidental findings in the first 2,000 clinical exomes assessed at that center since 2011 — a rate that's on par with the 5 percent or so described by other clinical sequencing centers. Some 3 percent of the cases contained incidental findings involving genes specifically mentioned in ACMG's guidelines, while the remaining 2 percent of the alterations that were deemed medically actionable fell in other genes.

Though the Baylor program does give patients an option of not receiving incidental findings for the genes falling outside of ACMG guidelines, Eng said that 96 percent of those patients sequenced so far have not opted out.

The University of Washington's Burke argued that patients are routinely offered choices about whether to receive or refuse care. From that perspective, she said, having the choice to find out about genetic alterations unrelated to the diagnostic question at hand would not be unusual.

In that situation, Burke said, it would be up to a physician to communicate potential risks or benefits of learning about disease risk not directly related to the condition for which exome or genome sequencing was originally requested.

For his part, Nussbaum noted that physicians have been faced with dilemmas about what information they should be conveying to patients long before whole-genome and whole-exome sequencing started making their way into the clinic.

The panel also touched on the controversy associated with informing parents about genetic glitches detected in ACMG 56 genes when sequencing is done on children, since the set includes some genes implicated in adult-onset conditions. Wolf commended ACMG for tackling the question of incidental findings in the first place, but said that feedback on certain pieces of the policy — including questions related to incidental findings in children — may prompt further changes to the guidelines.

In terms of the practicality of offering an opt-out from incidental findings, meanwhile, Evans argued that it would be far more effective to implement such opt-outs at the analytical stage rather than after genetic data has already made its way into an individual's electronic medical records.

In a quick digital poll of conference attendees listening to the panel, the majority of respondents said they favored future modifications to the ACMG guidelines.

In particular, nearly 90 percent said they would find it acceptable to offer patients the choice of opting out of information on the ACMG 56 genes. A slightly higher proportion said they would agree with allowing parents to opt out of receiving incidental findings related to adult-onset conditions for their children.

Just under half of attendees who responded by text or e-mail during the session said the guidelines would benefit from modifications that made it possible for patients to receive information on some but not all of the 56 genes.