Format

Send to

Choose Destination
Hum Mutat. 2018 Nov;39(11):1677-1685. doi: 10.1002/humu.23631.

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

Author information

1
Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon.
2
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
3
Genomic Medicine Institute, Geisinger, Danville, Pennsylvania.
4
Division of Genomics and Society, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
5
Department of Genetics, Stanford University, Stanford, California.
6
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina.
7
Department of Health Science Research, Mayo Clinic Arizona, Scottsdale, Arizona.
8
Autism & Developmental Medicine Institute, Geisinger, Danville, Pennsylvania.
9
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
10
Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
11
Institute for Human Genetics, University of California, San Francisco, San Francisco, California.
12
Department of Pediatrics, University of California, San Francisco, San Francisco, California.
13
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
14
American College of Medical Genetics and Genomics, Bethesda, Maryland.

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.

KEYWORDS:

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

PMID:
30311382
PMCID:
PMC6211797
DOI:
10.1002/humu.23631
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center