ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7610A>G (p.His2537Arg) (rs80358988)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000045257 SCV000073270 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-06-24 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 2537 of the BRCA2 protein (p.His2537Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the Breast Cancer Information Core database (PMID: 10923033). However, in that individual, a pathogenic allele was also identified in a the BRCA1 gene, which suggests that this c.7610A>G variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 52360). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). However, an algorithm developed specifically for the BRCA2 gene (PMID: 19043619), suggests that this missense change is likely to be tolerated. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and has been reported in an affected individual, it co-occurred with a pathogenic variant likely to explain the disease of that individual. The available evidence is currently insufficient to determine the role of this variant in disease, therefore it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000573982 SCV000668712 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759662 SCV000889136 uncertain significance not provided 2018-06-28 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113792 SCV000147145 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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