ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7643A>G (p.His2548Arg) (rs80358992)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129573 SCV000184355 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000031694 SCV000147154 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Invitae RCV000045275 SCV000073288 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-01-02 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 2548 of the BRCA2 protein (p.His2548Arg). 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 not been reported in the literature in individuals with a BRCA2-related disease. This variant has been reported in an individual in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 38112). 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. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000031694 SCV000054301 uncertain significance Breast-ovarian cancer, familial 2 2007-03-06 no assertion criteria provided clinical testing

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