ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7481G>A (p.Arg2494Gln) (rs80358973)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164832 SCV000215515 likely benign Hereditary cancer-predisposing syndrome 2017-10-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Co-occurence with mutation in same gene (phase unknown),Other data supporting benign classification
Breast Cancer Information Core (BIC) (BRCA2) RCV000083135 SCV000147103 uncertain significance Breast-ovarian cancer, familial 2 1999-06-22 no assertion criteria provided clinical testing
Color RCV000164832 SCV000911246 likely benign Hereditary cancer-predisposing syndrome 2017-04-19 criteria provided, single submitter clinical testing
GeneDx RCV000478347 SCV000567831 uncertain significance not provided 2018-08-28 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7481G>A at the cDNA level, p.Arg2494Gln (R2494Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). Using alternate nomenclature, this variant would be defined as BRCA2 7709G>A. This variant has been observed in at least two individuals with suspected Hereditary Breast and Ovarian Cancer syndrome (Santarosa 1999, Apessos 2018). In an in vitro assay, the variant demonstrated homology-directed repair activity comparable to wild-type (Guidugli 2018). BRCA2 Arg2494Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the DNA and FANCD2 binding domains (Yang 2002, UniProt). 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, it is unclear whether BRCA2 Arg2494Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Mendelics RCV000709331 SCV000838853 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083135 SCV000115209 likely benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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