title: Recommendations for returning genomic incidental findings? We need to talk!
abstract: The American College of Medical Genetics and Genomics recently issued recommendations for reporting incidental findings from clinical whole-genome sequencing and whole-exome sequencing. The recommendations call for evaluating a specific set of genes as part of all whole-genome sequencing/whole-exome sequencing and reporting all pathogenic variants irrespective of patient age. The genes are associated with highly penetrant disorders for which treatment or prevention is available. The effort to generate a list of genes with actionable findings is commendable, but the recommendations raise several concerns. They constitute a call for opportunistic screening, through intentional effort to identify pathogenic variants in specified genes unrelated to the clinical concern that prompted testing. Yet for most of the genes, we lack evidence about the predictive value of testing, genotype penetrance, spectrum of phenotypes, and efficacy of interventions in unselected populations. Furthermore, the recommendations do not allow patients to decline the additional findings, a position inconsistent with established norms. Finally, the recommendation to return adult-onset disease findings when children are tested is inconsistent with current professional consensus, including other policy statements of the American College of Medical Genetics and Genomics. Instead of premature practice recommendations, we call for robust dialogue among stakeholders to define a pathway to normatively sound, evidence-based guidelines.
authors.affiliation: Department of Bioethics and Humanities, University of Washington, Seattle, Washington, USA.
authors.forename: Wylie
authors.initials: W
authors.lastname: Burke
authors.forename: Armand H Matheny
authors.initials: AH
authors.lastname: Antommaria
authors.forename: Robin
authors.initials: R
authors.lastname: Bennett
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Botkin
authors.forename: Ellen Wright
authors.initials: EW
authors.lastname: Clayton
authors.forename: Gail E
authors.initials: GE
authors.lastname: Henderson
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Holm
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
authors.forename: Muin J
authors.initials: MJ
authors.lastname: Khoury
authors.forename: Bartha Maria
authors.initials: BM
authors.lastname: Knoppers
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Press
authors.forename: Lainie Friedman
authors.initials: LF
authors.lastname: Ross
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rothstein
authors.forename: Howard
authors.initials: H
authors.lastname: Saal
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Uhlmann
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wilfond
authors.forename: Susan M
authors.initials: SM
authors.lastname: Wolf
authors.forename: Ron
authors.initials: R
authors.lastname: Zimmern
mesh_terms: D000328:Adult; D002648:Child; D059472:Exome; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005826:Genetics, Medical; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D033162:Incidental Findings; D057240:Patient Preference; D028701:Patient Rights; D019683:Penetrance; D017410:Practice Guidelines as Topic; D017422:Sequence Analysis, DNA
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