ArticleNature communications2020
High-throughput functional evaluation of BRCA2 variants of unknown significance.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Systematic functional evaluation of CNGA1 missense variants associated with retinitis pigmentosa.Molecular medicine (Cambridge, Mass.) · 2026Article
- Comprehensive evidence for the pathogenicity of theJournal of medical genetics · 2026Article
- Functional assays for BRCA1 and BRCA2 variant analysis: new tools and their applications.NPJ breast cancer · 2026Review
- The functional landscape of coding variation in the familial hypercholesterolemia geneScience (New York, N.Y.) · 2026Article
- Site-saturation functional screens identify PALB2 missense variants associated with increased breast cancer risk.Nature communications · 2026Article
- The Performance ofHuman mutation · 2026Article
- Understanding the genetic epidemiology of hereditary breast cancer in India using whole genome data from 1029 healthy individuals.Cancer causes & control : CCC · 2025Article
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- GLI1 confers resistance to PARP inhibitors by activating the DNA damage repair pathway.Oncogene · 2024Article
- Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset.American journal of human genetics · 2024Article
- Functional analysis and clinical classification of 462 germline BRCA2 missense variants affecting the DNA binding domain.American journal of human genetics · 2024Article
- Functional evaluation of BRCA1/2 variants of unknown significance with homologous recombination assay and integrative in silico prediction model.Journal of human genetics · 2023Article
- Performance of a RAD51-based functional HRD test on paraffin-embedded breast cancer tissue.Breast cancer research and treatment · 2023Article
- Sequencing-based functional assays for classification of BRCA2 variants in mouse ESCs.Cell reports methods · 2023Article
- Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer.JAMA oncology · 2023Article
- Personalized medicine with germline pathogenic variants: Importance of population- and region-wide evidence.Cancer science · 2023Review
- Saturation genome editing of 11 codons and exon 13 of BRCA2 coupled with chemotherapeutic drug response accurately determines pathogenicity of variants.PLoS genetics · 2023Article
- The pathogenic role of the BRCA2 c.7847C>T (p.Ser2616Phe) variant in breast and ovarian cancer predisposition.Cancer science · 2023Article
- Estimating clinical risk in gene regions from population sequencing cohort data.American journal of human genetics · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous nontruncating missense variants of the BRCA2 gene have been identified, but there is a lack of convincing evidence, such as familial data, demonstrating their clinical relevance and they thus remain unactionable. To assess the pathogenicity of variants of unknown significance (VUSs) within BRCA2, here we develop a method, the MANO-B method, for high-throughput functional evaluation utilizing BRCA2-deficient cells and poly (ADP-ribose) polymerase (PARP) inhibitors. The estimated sensitivity and specificity of this assay compared to those of the International Agency for Research on Cancer classification system is 95% and 95% (95% confidence intervals: 77-100% and 82-99%), respectively. We classify the functional impact of 186 BRCA2 VUSs with our computational pipeline, resulting in the classification of 126 variants as normal/likely normal, 23 as intermediate, and 37 as abnormal/likely abnormal. We further describe a simplified, on-demand annotation system that could be used as a companion diagnostic for PARP inhibitors in patients with unknown BRCA2 VUSs.
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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.