Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun;24(6):1328-1335.
doi: 10.1016/j.gim.2022.02.019. Epub 2022 Mar 25.

ClinGen's Pediatric Actionability Working Group: Clinical actionability of secondary findings from genome-scale sequencing in children and adolescents

Jessica Ezzell Hunter  1 , Charisma L Jenkins  2 , Joanna E Bulkley  2 , Marian J Gilmore  2 , Kristy Lee  3 , Christine M Pak  2 , Kathleen E Wallace  3 , Adam H Buchanan  4 , Ann Katherine M Foreman  3 , Amanda S Freed  5 , Scott Goehringer  4 , Kandamurugu Manickam  6 , Naomi J L Meeks  7 , Erin M Ramos  8 , Neethu Shah  9 , Robert D Steiner  10 , Sai Lakshmi Subramanian  9 , Tracy Trotter  11 , Elizabeth M Webber  12 , Marc S Williams  4 , Katrina A B Goddard  2 , Bradford C Powell  3 ; ClinGen
Affiliations

ClinGen's Pediatric Actionability Working Group: Clinical actionability of secondary findings from genome-scale sequencing in children and adolescents

Jessica Ezzell Hunter et al. Genet Med. 2022 Jun.

Abstract

Purpose: Synthesis and curation of evidence regarding the clinical actionability of secondary findings (SFs) from genome-scale sequencing are needed to support decision-making on reporting of these findings. To assess actionability of SFs in children and adolescents, the Clinical Genome Resource established the Pediatric Actionability Working Group (AWG).

Methods: The Pediatric AWG modified the framework of the existing Adult AWG, which included production of summary reports of actionability for genes and associated conditions and consensus actionability scores for specific outcome-intervention pairs. Modification of the adult framework for the pediatric setting included accounting for special considerations for reporting presymptomatic or predictive genetic findings in the pediatric context, such as maintaining future autonomy by not disclosing conditions not actionable until adulthood. The Pediatric AWG then applied this new framework to genes and associated conditions with putative actionability.

Results: As of September 2021, the Pediatric AWG applied the new framework to 70 actionability topics representing 143 genes. Reports and scores are publicly available at www.clinicalgenome.org.

Conclusion: The Pediatric AWG continues to curate gene-condition topics and build an evidence-based resource, supporting clinical communities and decision-makers with policy development on the return of SFs in pediatric populations.

Keywords: Clinical actionability; Exome sequencing; Genome sequencing; Pediatrics; Secondary findings.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest R.D.S. has equity interest in and has received consulting fees from Acer Inc and PTC Therapeutics. He has received consulting fees from Aeglea BioTherapeutics; Alexion Pharmaceuticals, Inc; Best Doctors; Health Advances LLC; Precision for Value; and Travere Therapeutics, Inc; and honoraria from Medscape/WebMD LLC and The France Foundation. R.D.S. is an employee of PreventionGenetics. He received research funding from Alexion Pharmaceuticals, Inc and the Smith Lemli Opitz Foundation. All other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Distribution of Highest Scoring Outcome-Intervention Pairs from Gene-Condition Topics Assessed by the Pediatric AWG
Figure 2.
Figure 2.
Distribution of Actionability Domain Scores for Highest Scoring Outcome–Intervention Pairs from Gene-Condition Topics Assessed by the Pediatric AWG
See this image and copyright information in PMC

References

    1. Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014;370(25):2418–2425. - PubMed
    1. US Presidential Commission for the Study of Bioethical Issues. Anticipate and communicate: ethical management of incidental and secondary findings in the clinical, research, and direct-to-consumer contexts. Washington, DC: Presidential Commission for the Study of Bioethical Issues;2013. - PubMed
    1. Jarvik GP, Amendola LM, Berg JS, et al. Return of genomic results to research participants: the floor, the ceiling, and the choices in between. Am J Hum Genet. 2014;94(6):818–826. - PMC - PubMed
    1. Rehm HL, Berg JS, Brooks LD, et al. ClinGen--the clinical genome resource. N Engl J Med. 2015;372(23):2235–2242. - PMC - PubMed
    1. Hunter JE, Irving SA, Biesecker LG, et al. A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation. Genet Med. 2016;18(12):1258–1268. - PMC - PubMed

Publication types

LinkOut - more resources