Evidence-based assessments of clinical actionability in the context of secondary findings: Updates from ClinGen's Actionability Working Group

on behalf of the ClinGen Resource

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The use of genome-scale sequencing allows for identification of genetic findings beyond the original indication for testing (secondary findings). The ClinGen Actionability Working Group's (AWG) protocol for evidence synthesis and semi-quantitative metric scoring evaluates four domains of clinical actionability for potential secondary findings: severity and likelihood of the outcome, and effectiveness and nature of the intervention. As of February 2018, the AWG has scored 127 genes associated with 78 disorders (up-to-date topics/scores are available at www.clinicalgenome.org). Scores across these disorders were assessed to compare genes/disorders recommended for return as secondary findings by the American College of Medical Genetics and Genomics (ACMG) with those not currently recommended. Disorders recommended by the ACMG scored higher on outcome-related domains (severity and likelihood), but not on intervention-related domains (effectiveness and nature of the intervention). Current practices indicate that return of secondary findings will expand beyond those currently recommended by the ACMG. The ClinGen AWG evidence reports and summary scores are not intended as classifications of actionability, rather they provide a resource to aid decision makers as they determine best practices regarding secondary findings. The ClinGen AWG is working with the ACMG Secondary Findings Committee to update future iterations of their secondary findings list.

Original languageEnglish (US)
Pages (from-to)1677-1685
Number of pages9
JournalHuman mutation
Volume39
Issue number11
DOIs
StatePublished - Nov 2018

Keywords

  • clinical utility
  • exome sequencing
  • genome sequencing
  • incidental findings
  • secondary findings

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Evidence-based assessments of clinical actionability in the context of secondary findings: Updates from ClinGen's Actionability Working Group'. Together they form a unique fingerprint.

  • Cite this