A Standardized Framework to Assess the Clinical Actionability of Genes and Associated Conditions for Population-Based Genomic Screening
9 affiliations
- 1Center for Genomics and Applied Public Health, RTI International, Research Triangle Park, NC, USA
- 2Department of Implementation Science, Wake Forest University School of Medicine, Winston Salem, NC, USA
- 3Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
- 4Department of Behavioral, Social, and Health Education Sciences, Rollins School of Public Health, Emory University, Atlanta, GA, USA
- 5Case Western Reserve University School of Medicine, Cleveland, OH, USA
- 6Emory University, Atlanta, GA, USA
- 7Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH, USA
- 8Department of Population Medicine, Harvard Medical School, Boston, MA, USA
- 9Department of Genomic Health, Geisinger, Danville, PA, USA
Abstract
Introduction: As population-based genomic screening (PGS) programs are increasingly implemented, standardized, evidence-based approaches are needed to support decision-making about which genetic findings should be returned based on clinical actionability. The Clinical Genome Resource (ClinGen) Actionability Framework, which guides decision-making on the return of monogenic secondary findings, was adapted to create a framework for the context of PGS in adults.
Methods: ClinGen convened a group of experts in public health, medical genetics and genomics, genetic counseling, population screening, health economics, and bioethics. Adaptation of the ClinGen Actionability Framework included special considerations for reporting genetic findings in the PGS context, such as screening in unselected populations, penetrance certainty, and cost-effectiveness. Several frameworks relevant to PGS, including public health decision-making and bioethics frameworks, were reviewed, and items were abstracted. For items deemed relevant to the PGS context, a thematic clustering method was used to group similar items into conceptually related clusters. Through an iterative process of discussion and consensus building, the clusters were reviewed, refined, and used to define domains of actionability specific to the PGS context. These final domains were selected based on conceptual clarity, distinctiveness, and their relevance to decision-making about the return of genomic findings in unselected populations.
Results: The ClinGen PGS Actionability Framework includes a set of expanded domains that integrate clinical and public health perspectives on actionability while preserving alignment with the original structure and purpose of the ClinGen AWG framework. The framework guides the review and curation of evidence of actionability for genes and associated conditions, consensus scores for domains of actionability for specific outcome-intervention pairs, and assertions on the level of actionability.
Conclusion: The ClinGen PGS Actionability Framework provides an evidence-based resource to support clinical communities and decision-makers with policy development on the return of genetic findings in PGS programs.
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BibTeX
@article{hunter2026standardized,
title = {{A Standardized Framework to Assess the Clinical Actionability of Genes and Associated Conditions for Population-Based Genomic Screening}},
author = {Jessica Ezzell Hunter and Caitlin G. Allen and Jonathan S. Berg and W. David Dotson and Kimberly S. Foss and Aaron J. Goldenberg and Yue Guan and Christina Gutierrez-Ford and Kandamurugu Manickam and Hadley Stevens Smith and Adam H. Buchanan},
journal = {Public Health Genomics},
year = {2026},
month = sep,
doi = {10.1159/phg/aenag002},
url = {https://doi.org/10.1159/phg/aenag002},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - A Standardized Framework to Assess the Clinical Actionability of Genes and Associated Conditions for Population-Based Genomic Screening
AU - Jessica Ezzell Hunter
AU - Caitlin G. Allen
AU - Jonathan S. Berg
AU - W. David Dotson
AU - Kimberly S. Foss
AU - Aaron J. Goldenberg
AU - Yue Guan
AU - Christina Gutierrez-Ford
AU - Kandamurugu Manickam
AU - Hadley Stevens Smith
AU - Adam H. Buchanan
PY - 2026
DA - 2026/09/22
JO - Public Health Genomics
DO - 10.1159/phg/aenag002
UR - https://doi.org/10.1159/phg/aenag002
AB - Introduction: As population-based genomic screening (PGS) programs are increasingly implemented, standardized, evidence-based approaches are needed to support decision-making about which genetic findings should be returned based on clinical actionability. The Clinical Genome Resource (ClinGen) Actionability Framework, which guides decision-making on the return of monogenic secondary findings, was adapted to create a framework for the context of PGS in adults. Methods: ClinGen convened a group of experts in public health, medical genetics and genomics, genetic counseling, population screening, health economics, and bioethics. Adaptation of the ClinGen Actionability Framework included special considerations for reporting genetic findings in the PGS context, such as screening in unselected populations, penetrance certainty, and cost-effectiveness. Several frameworks relevant to PGS, including public health decision-making and bioethics frameworks, were reviewed, and items were abstracted. For items deemed relevant to the PGS context, a thematic clustering method was used to group similar items into conceptually related clusters. Through an iterative process of discussion and consensus building, the clusters were reviewed, refined, and used to define domains of actionability specific to the PGS context. These final domains were selected based on conceptual clarity, distinctiveness, and their relevance to decision-making about the return of genomic findings in unselected populations. Results: The ClinGen PGS Actionability Framework includes a set of expanded domains that integrate clinical and public health perspectives on actionability while preserving alignment with the original structure and purpose of the ClinGen AWG framework. The framework guides the review and curation of evidence of actionability for genes and associated conditions, consensus scores for domains of actionability for specific outcome-intervention pairs, and assertions on the level of actionability. Conclusion: The ClinGen PGS Actionability Framework provides an evidence-based resource to support clinical communities and decision-makers with policy development on the return of genetic findings in PGS programs.
SN - 1662-4246
SN - 1662-8063
ER -