ArticleGenetics in medicine : official journal of the American College of Medical Genetics2016
A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03548779 (North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2), which is not on this map. Cited by 57 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
Who cites it
57 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Evaluating whole genome sequencing for rare diseases in newborn screening: evidence synthesis from a series of systematic reviews.Health technology assessment (Winchester, England) · 2025Pooled it
- Principles of Genomic Newborn Screening Programs: A Systematic Review.JAMA network open · 2021Pooled it
- Evidence for penetrance in patients without a family history of disease: a systematic review.European journal of human genetics : EJHG · 2020Pooled it
- Short-term costs of integrating whole-genome sequencing into primary care and cardiology settings: a pilot randomized trial.Genetics in medicine : official journal of the American College of Medical Genetics · 2018Trial
- The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial.Annals of internal medicine · 2017Trial
- Newborn Sequencing in Genomic Medicine and Public Health.Pediatrics · 2017Trial
- When bins blur: Patient perspectives on categories of results from clinical whole genome sequencing.AJOB empirical bioethicsTrial
- Recommendations for return of secondary genomic findings in observational cohort studies.Nature genetics · 2026Review
- To screen or not to screen G6PD deficiency in gNBS: insights from the BabyDetect pilot and current evidence.European journal of human genetics : EJHG · 2026Article
- Returning of individual genetic findings to biobank participants: a mixed methods study results in Lithuania.BMC medical ethics · 2025Article
- Data-driven consideration of genetic disorders for global genomic newborn screening programs.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- How people undergoing genomic sequencing interpret and react to varied secondary findings with limited actionability.Personalized medicine · 2025Article
- Actionability of Genetic Variants in Diabetes: Core Aspects and Applied Examples.Diabetes spectrum : a publication of the American Diabetes Association · 2025Article
- The Clinical Genome Resource (ClinGen): Advancing genomic knowledge through global curation.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Wilson and Jungner Revisited: Are Screening Criteria Fit for the 21st Century?International journal of neonatal screening · 2024Review
- A framework for the evaluation and reporting of incidental findings in clinical genomic testing.European journal of human genetics : EJHG · 2024Article
- The GenoVA study: Equitable implementation of a pragmatic randomized trial of polygenic-risk scoring in primary care.American journal of human genetics · 2023Article
- Actionability of unanticipated monogenic disease risks in newborn genomic screening: Findings from the BabySeq Project.American journal of human genetics · 2023Article
- Age-Based Genomic Screening during Childhood: Ethical and Practical Considerations in Public Health Genomics Implementation.International journal of neonatal screening · 2023Article
- How Clinicians Conceptualize "Actionability" in Genomic Screening.Journal of personalized medicine · 2023Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
purposeAs genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, necessitating standardized frameworks for a priori decision making about their analysis.
methodsWe established a semiquantitative metric to assess five elements of actionability: severity and likelihood of the disease outcome, efficacy and burden of intervention, and knowledge base, with a total score from 0 to 15.
resultsThe semiquantitative metric was applied to a list of putative actionable conditions, the list of genes recommended by the American College of Medical Genetics and Genomics (ACMG) for return when deleterious variants are discovered as secondary/incidental findings, and a random sample of 1,000 genes. Scores from the list of putative actionable conditions (median = 12) and the ACMG list (median = 11) were both statistically different than the randomly selected genes (median = 7) (P < 0.0001, two-tailed Mann-Whitney test).
conclusionGene-disease pairs having a score of 11 or higher represent the top quintile of actionability. The semiquantitative metric effectively assesses clinical actionability, promotes transparency, and may facilitate assessments of clinical actionability by various groups and in diverse contexts.Genet Med 18 5, 467-475.
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