ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7505G>C (p.Arg2502Pro) (rs56070345)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000697931 SCV000826565 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-02-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 2502 of the BRCA2 protein (p.Arg2502Pro). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 126139). An algorithm developed specifically for the BRCA2 gene suggests that this missense change is likely to be tolerated (PMID: 19043619). However, this prediction has not been confirmed by published functional studies and its clinical significance is uncertain. In summary, 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.
Integrated Genetics/Laboratory Corporation of America RCV000781093 SCV000918911 uncertain significance not specified 2018-06-22 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.7505G>C (p.Arg2502Pro) results in a non-conservative amino acid change located in the Breast cancer type 2 susceptibility protein, helical domain (IPR015252) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 246182 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.7505G>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113770 SCV000147110 uncertain significance Breast-ovarian cancer, familial 2 2001-10-29 no assertion criteria provided clinical testing

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