ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.526A>T (p.Thr176Ser)

dbSNP: rs1214427273
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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 RCV001055619 SCV001220019 uncertain significance Hereditary breast ovarian cancer syndrome 2023-10-15 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 176 of the BRCA2 protein (p.Thr176Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 851261). 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. 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.
Liquid Biopsy and Cancer Interception Group, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research RCV001090207 SCV001245505 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 criteria provided, single submitter clinical testing
Ambry Genetics RCV002348413 SCV002642608 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-21 criteria provided, single submitter clinical testing The p.T176S variant (also known as c.526A>T), located in coding exon 6 of the BRCA2 gene, results from an A to T substitution at nucleotide position 526. The threonine at codon 176 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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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