ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3200C>G (p.Thr1067Ser)

dbSNP: rs1555283092
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000551092 SCV000635274 uncertain significance Hereditary breast ovarian cancer syndrome 2019-07-04 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 1067 of the BRCA2 protein (p.Thr1067Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA2-related conditions.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157654 SCV003851761 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics RCV003157654 SCV004052551 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-07 criteria provided, single submitter clinical testing The p.T1067S variant (also known as c.3200C>G), located in coding exon 10 of the BRCA2 gene, results from a C to G substitution at nucleotide position 3200. The threonine at codon 1067 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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