ArticleNPJ precision oncology2024
Reduced penetrance BRCA1 and BRCA2 pathogenic variants in clinical germline genetic testing.
Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Consideration of inherited cancer risk on a continuum: An international and multidisciplinary perspective: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2026Guideline
- Genotype-phenotype correlations inOncology reviews · 2025Pooled it
- Domain-Specific Computational, Functional and Structural Methods Enable Interpretation ofCurrent oncology (Toronto, Ont.) · 2026Article
- Integrating enriched case data from national laboratory testing with population-based case-control analyses: a novel statistical likelihood-ratio methodology for PS4 applied to 325,345 breast cancer cases and 671,006 controls.medRxiv : the preprint server for health sciences · 2026Article
- Refining breast cancer risk estimation in carriers of pathogenicTranslational cancer research · 2026Article
- Functional assays for BRCA1 and BRCA2 variant analysis: new tools and their applications.NPJ breast cancer · 2026Review
- Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma.Nature communications · 2026Article
- GermlineCurrent oncology (Toronto, Ont.) · 2025Article
- The Risk of Breast Cancer According to Mutation Type and Position in Carriers of a Pathogenic Variant inCurrent oncology (Toronto, Ont.) · 2025Article
- BRCA1-, BRCA2-, and PALB2-related Fanconi anemia: Scope to expand disease phenotypic features and predict breast cancer risk in heterozygotes.American journal of human genetics · 2025Article
- Preventive Measures for Patients with an Elevated Genetic Risk for Gynecological Malignancies, in Particular Familial Breast and Ovarian Cancer.Deutsches Arzteblatt international · 2025Review
- Identification and Computational Analysis ofMedical sciences (Basel, Switzerland) · 2025Article
- Recontact and follow-up for individuals with germline pathogenic variants in hereditary breast and ovarian cancer susceptibility genes: a UK Cancer Genetics Group consensus meeting.Journal of medical genetics · 2025Article
- When two plus four does not equal six: Combining computational and functional evidence to classify BRCA1 key domain missense substitutions.American journal of human genetics · 2025Article
- Pathonign variants in recessive disorders: How extremely hypomorphic variants can be pathogenic and benign depending on the allele in trans.Intractable & rare diseases research · 2025Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Prior studies have suggested the existence of reduced penetrance pathogenic variants (RPPVs) in BRCA1 and BRCA2 (BRCA) which pose challenges for patient counseling and care. Here, we sought to establish RPPVs as a new category of variants. Candidate BRCA RPPVs provided by two large clinical diagnostic laboratories were compiled to identify those with the highest likelihood of being a RPPV, based on concordant interpretations. Sixteen concordant candidate BRCA RPPVs across both laboratories were systematically assessed. RPPVs included missense, splice site, and frameshift variants. Our study establishes RPPVs as a new class of variants imparting a moderately increased risk of breast cancer, which impacts risk-informed cancer prevention strategies, and provides a framework to standardize interpretation and reporting of BRCA RPPVs. Further work to define clinically meaningful risk thresholds and categories for reporting BRCA RPPVs is needed to personalize cancer risks in conjunction with other risk factors.
Identifiers
What OpenQuestion holds
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.