ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7976G>C (p.Arg2659Thr) (rs80359027)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113849 SCV000244477 pathogenic Breast-ovarian cancer, familial 2 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 0.997
Color Health, Inc RCV000583576 SCV000689086 pathogenic Hereditary cancer-predisposing syndrome 2020-10-12 criteria provided, single submitter clinical testing This missense variant replaces arginine with threonine at codon 2659 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional RNA studies have shown that this variant causes skpping of exon 17 and reduced DNA repair activity (PMID: 18451181). This variant has been reported in individuals affected with breast/ovarian cancer in the literature (PMID: 16489001, 25447315). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113849 SCV000147236 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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