ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7964A>G (p.Gln2655Arg) (rs80359024)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000510118 SCV000608034 likely pathogenic Hereditary cancer-predisposing syndrome 2018-02-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s),Structural Evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other data supporting pathogenic classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000113846 SCV000147229 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Color RCV000510118 SCV000911874 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-07 criteria provided, single submitter clinical testing
Counsyl RCV000113846 SCV000785547 uncertain significance Breast-ovarian cancer, familial 2 2017-09-06 criteria provided, single submitter clinical testing
GeneDx RCV000212265 SCV000210453 likely pathogenic not provided 2018-03-07 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7964A>G at the cDNA level, p.Gln2655Arg (Q2655R) at the protein level, and results in the change of a Glutamine to an Arginine (CAA>CGA). Using alternate nomenclature, this variant would be defined as BRCA2 8192A>G. Ruud et al. (2001) reported a patient with Fanconi anemia who passed away following a diagnosis of medulloblastoma and resultant chemotherapy toxicity. Follow-up studies on archived tissue by Bodd et al. (2010) revealed compound heterozygosity for BRCA2 Gln2655Arg, present in her father, and a BRCA2 nonsense variant, present in her mother, who had a family history of breast and ovarian cancer. In addition, functional studies of this variant showed decreased homology directed repair activity (Guidugli 2018). BRCA2 Gln2655Arg was not observed in large population cohorts (Lek 2016). BRCA2 Gln2655Arg is located in the DNA binding domain and the DSS1 contacting residue (Yang 2002). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, we consider BRCA2 Gln2655Arg to be likely pathogenic.

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