ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Considerations for clinical curation, classification, and reporting of low-penetrance and low effect size variants associated with disease risk.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis 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.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Systematic Review and Recommendations Around Frameworks for Evaluating Scientific Validity in Nutritional Genomics.Frontiers in nutrition · 2021Pooled it
- Patient Perspectives on Psychiatric Polygenic Risk Scores in Reproductive Decision-Making and Polygenic Embryo Screening.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2026Article
- Case-Control Study for 23 Cancer Types With Functional Analysis ofJCO precision oncology · 2025Article
- 2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.Neurobiology of disease · 2025Review
- Review
- Elective genomic screening: results of the implementation of a whole genome sequencing program at a medical check-up unit in Spain.Frontiers in genetics · 2025Article
- Reduced penetrance BRCA1 and BRCA2 pathogenic variants in clinical germline genetic testing.NPJ precision oncology · 2024Article
- Genetically transitional disease: conceptual understanding and applicability to rheumatic disease.Nature reviews. Rheumatology · 2024Review
- Amyopathic dermatomyositis may be on the spectrum of autoinflammatory disease: A clinical review.Rheumatology and immunology research · 2024Review
- Recommendations for risk allele evidence curation, classification, and reporting from the ClinGen Low Penetrance/Risk Allele Working Group.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Ancestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments.Nature communications · 2023Article
- The GenoVA study: Equitable implementation of a pragmatic randomized trial of polygenic-risk scoring in primary care.American journal of human genetics · 2023Article
- Germ line variants in patients with acute myeloid leukemia without a suspicion of hereditary hematologic malignancy syndrome.Blood advances · 2023Article
- Genetic variations in NLRP3 and NLRP12 genes in adult-onset patients with autoinflammatory diseases: a comparative study.Frontiers in immunology · 2023Article
- Implications of combinedFrontiers in immunology · 2023Article
- The CommonHuman mutation · 2023Article
- Calculating variant penetrance from family history of disease and average family size in population-scale data.Genome medicine · 2022Article
- A founder event causing a dominant childhood epilepsy survives 800 years through weak selective pressure.American journal of human genetics · 2022Article
- Development of a clinical polygenic risk score assay and reporting workflow.Nature medicine · 2022Article
- Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts.Frontiers in genetics · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeClinically relevant variants exhibit a wide range of penetrance. Medical practice has traditionally focused on highly penetrant variants with large effect sizes and, consequently, classification and clinical reporting frameworks are tailored to that variant type. At the other end of the penetrance spectrum, where variants are often referred to as "risk alleles," traditional frameworks are no longer appropriate. This has led to inconsistency in how such variants are interpreted and classified. Here, we describe a conceptual framework to begin addressing this gap.
methodsWe used a set of risk alleles to define data elements that can characterize the validity of reported disease associations. We assigned weight to these data elements and established classification categories expressing confidence levels. This framework was then expanded to develop criteria for inclusion of risk alleles on clinical reports.
resultsFoundational data elements include cohort size, quality of phenotyping, statistical significance, and replication of results. Criteria for determining inclusion of risk alleles on clinical reports include presence of clinical management guidelines, effect size, severity of the associated phenotype, and effectiveness of intervention.
conclusionThis framework represents an approach for classifying risk alleles and can serve as a foundation to catalyze community efforts for refinement.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.