ArticleAmerican journal of human genetics2024
Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel.
Article in American journal of human genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed.
- Impact of mainstream genetic testing for breast cancer patients: five-year data from the Parkville Familial Cancer Centre.Familial cancer · 2026Article
- Clinical impact of ENIGMA-based variant reclassification on genotype-phenotype analyses in BRCA1- and BRCA2-associated hereditary breast and ovarian cancer.Breast cancer (Tokyo, Japan) · 2026Article
- Pathogenicity assessment of genetic variants in reproductive disorders.Journal of assisted reproduction and genetics · 2026Review
- Minigene-based characterization and classification of splice-associated variants in succinate dehydrogenase B.NPJ precision oncology · 2026Article
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Updated ENIGMA recommendations for reporting germline variants in cancer susceptibility genes and their translation into twenty languages.Journal of medical genetics · 2026Article
- A prioritization framework for BRCA1/2 variants of uncertain significance identified by comprehensive genomic profiling.European journal of human genetics : EJHG · 2026Article
- BRCA1 and BRCA2 population screening in Latvia: feasibility, engagement, and early lessons from a pilot study.European journal of human genetics : EJHG · 2026Article
- PARP Inhibitor Sensitivity in Tumors Harboring Non-BRCA Homologous Recombination Gene Alterations: Current Evidence Across Ovarian, Breast, Prostate, and Pancreatic Cancers.International journal of molecular sciences · 2026Review
- Combining multiplexed functional data to improve variant classification.Genome medicine · 2026Article
- Reclassification of a BRCA2 variant, c.8487G > A (p.Gln2829Gln) located at 3' end of exon 19, from uncertain significance to likely pathogenic based on splicing alteration: a case report.Japanese journal of clinical oncology · 2026Article
- Review
- Comprehensive evidence for the pathogenicity of theJournal of medical genetics · 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
- Article
- Gene- and domain-aware calibration increases the clinical utility of variant effect predictors.Research square · 2026Article
- Transformative Applications and Innovations in Next-Generation Sequencing Data Analysis.Journal of applied genetics · 2026Review
- Functional assays for BRCA1 and BRCA2 variant analysis: new tools and their applications.NPJ breast cancer · 2026Review
- Combining multiplexed assays of variant effect for enhanced BRCA2 variant classification.Nature communications · 2026Article
- Integrating breast tumour homologous recombination deficiency status to aid germline BRCA1 and BRCA2 variant classification.EBioMedicine · 2026Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
43 authors.
Funding
Abstract
The ENIGMA research consortium develops and applies methods to determine clinical significance of variants in hereditary breast and ovarian cancer genes. An ENIGMA BRCA1/2 classification sub-group, formed in 2015 as a ClinGen external expert panel, evolved into a ClinGen internal Variant Curation Expert Panel (VCEP) to align with Food and Drug Administration recognized processes for ClinVar contributions. The VCEP reviewed American College of Medical Genetics and Genomics/Association of Molecular Pathology (ACMG/AMP) classification criteria for relevance to interpreting BRCA1 and BRCA2 variants. Statistical methods were used to calibrate evidence strength for different data types. Pilot specifications were tested on 40 variants and documentation revised for clarity and ease of use. The original criterion descriptions for 13 evidence codes were considered non-applicable or overlapping with other criteria. Scenario of use was extended or re-purposed for eight codes. Extensive analysis and/or data review informed specification descriptions and weights for all codes. Specifications were applied to pilot variants with pre-existing ClinVar classification as follows: 13 uncertain significance or conflicting, 14 pathogenic and/or likely pathogenic, and 13 benign and/or likely benign. Review resolved classification for 11/13 uncertain significance or conflicting variants and retained or improved confidence in classification for the remaining variants. Alignment of pre-existing ENIGMA research classification processes with ACMG/AMP classification guidelines highlighted several gaps in the research processes and the baseline ACMG/AMP criteria. Calibration of evidence strength was key to justify utility and strength of different data types for gene-specific application. The gene-specific criteria demonstrated value for improving ACMG/AMP-aligned classification of BRCA1 and BRCA2 variants.
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