ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.518G>T (p.Gly173Val) (rs28897702)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044598 SCV000072611 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-12-19 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 173 of the BRCA2 protein (p.Gly173Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs28897702, ExAC 0.01%). This variant has been reported in an individual affected with breast cancer (PMID: 25682074). However, in an individual in the Breast Cancer Information Core database (PMID: 10923033), a pathogenic allele was also identified in the BRCA1 gene, which suggests that this c.518G>T substitution in BRCA2 was not the primary cause of disease in this individual. ClinVar contains an entry for this variant (Variation ID: 51810). While experimental studies have shown that this variant has a conflicting effect on skipping exon 7 in splicing minigene assays (PMID: 23983145, 20215541), protein function on homologous recombination (HR) is preserved in HR-based assays (PMID: 21671020). In summary, this is a rare missense change that has been reported in affected individuals and has been shown to partially affect splicing. However, it has been also observed in the general population and has been shown to preserve protein function. For these reasons, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000213680 SCV000273887 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000113738 SCV000147058 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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