ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6263C>G (p.Thr2088Ser)

dbSNP: rs767567428
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001181099 SCV001346178 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001876017 SCV002176866 uncertain significance Hereditary breast ovarian cancer syndrome 2021-06-18 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 921599). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 2088 of the BRCA2 protein (p.Thr2088Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine.
University of Washington Department of Laboratory Medicine, University of Washington RCV001181099 SCV003852366 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 RCV001181099 SCV005551999 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-20 criteria provided, single submitter clinical testing The p.T2088S variant (also known as c.6263C>G), located in coding exon 10 of the BRCA2 gene, results from a C to G substitution at nucleotide position 6263. The threonine at codon 2088 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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