ArticleNPJ genomic medicine2020
A computational model for classification of BRCA2 variants using mouse embryonic stem cell-based functional assays.
Article in NPJ genomic medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Functional assays for BRCA1 and BRCA2 variant analysis: new tools and their applications.NPJ breast cancer · 2026Review
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- Article
- Article
- Reclassification of VUS inGenetics in medicine open · 2025Article
- Reduced penetrance BRCA1 and BRCA2 pathogenic variants in clinical germline genetic testing.NPJ precision oncology · 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
- Sequencing-based functional assays for classification of BRCA2 variants in mouse ESCs.Cell reports methods · 2023Article
- Saturation genome editing of 11 codons and exon 13 of BRCA2 coupled with chemotherapeutic drug response accurately determines pathogenicity of variants.PLoS genetics · 2023Article
- Rare germline variants in PALB2 and BRCA2 in familial and sporadic chordoma.Human mutation · 2022Article
- Article
- Classification of BRCA2 Variants of Uncertain Significance (VUS) Using an ACMG/AMP Model Incorporating a Homology-Directed Repair (HDR) Functional Assay.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- An integrative model for the comprehensive classification of BRCA1 and BRCA2 variants of uncertain clinical significance.NPJ genomic medicine · 2022Article
- BRCA2-DSS1 interaction is dispensable for RAD51 recruitment at replication-induced and meiotic DNA double strand breaks.Nature communications · 2022Article
- Genotype-cancer association in patients with Fanconi anemia due to pathogenic variants in FANCD1 (BRCA2) or FANCN (PALB2).Cancer genetics · 2021Article
- Fanconi Anaemia, Childhood Cancer and theGenes · 2021Review
- Review
- K3326X and Other C-Terminal BRCA2 Variants Implicated in Hereditary Cancer Syndromes: A Review.Cancers · 2021Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Sequencing-based genetic tests to identify individuals at increased risk of hereditary breast and ovarian cancers have resulted in the identification of more than 40,000 sequence variants of BRCA1 and BRCA2. A majority of these variants are considered to be variants of uncertain significance (VUS) because their impact on disease risk remains unknown, largely due to lack of sufficient familial linkage and epidemiological data. Several assays have been developed to examine the effect of VUS on protein function, which can be used to assess their impact on cancer susceptibility. In this study, we report the functional characterization of 88 BRCA2 variants, including several previously uncharacterized variants, using a well-established mouse embryonic stem cell (mESC)-based assay. We have examined their ability to rescue the lethality of Brca2 null mESC as well as sensitivity to six DNA damaging agents including ionizing radiation and a PARP inhibitor. We have also examined the impact of BRCA2 variants on splicing. In addition, we have developed a computational model to determine the probability of impact on function of the variants that can be used for risk assessment. In contrast to the previous VarCall models that are based on a single functional assay, we have developed a new platform to analyze the data from multiple functional assays separately and in combination. We have validated our VarCall models using 12 known pathogenic and 10 neutral variants and demonstrated their usefulness in determining the pathogenicity of BRCA2 variants that are listed as VUS or as variants with conflicting functional interpretation.
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.