ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.10186A>C (p.Ser3396Arg)

dbSNP: rs1555290062
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001176506 SCV001340505 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001304817 SCV001494116 uncertain significance Hereditary breast ovarian cancer syndrome 2022-07-14 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. ClinVar contains an entry for this variant (Variation ID: 433843). This missense change has been observed in individual(s) with breast cancer (PMID: 29884136). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 3396 of the BRCA2 protein (p.Ser3396Arg).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000503953 SCV000592315 uncertain significance not provided no assertion criteria provided clinical testing The BRCA2 p.Ser3396Arg variant was not identified in the literature but was identified in the COSMIC database in one case of endometrial carcinoma. The p.Ser3396 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD) do not suggest a high likelihood of impact of the p.Ser3396Arg variant to the protein. However, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of unknown significance.

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