ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1606T>A (p.Ser536Thr)

gnomAD frequency: 0.00001  dbSNP: rs1227088794
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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 RCV000805866 SCV000945839 uncertain significance Hereditary breast ovarian cancer syndrome 2020-03-31 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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 disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with threonine at codon 536 of the BRCA2 protein (p.Ser536Thr). The serine residue is moderately conserved and there is a small physicochemical difference between serine and threonine.
Ambry Genetics RCV002397639 SCV002706440 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-06 criteria provided, single submitter clinical testing The p.S536T variant (also known as c.1606T>A), located in coding exon 9 of the BRCA2 gene, results from a T to A substitution at nucleotide position 1606. The serine at codon 536 is replaced by threonine, 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002397639 SCV003851520 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).

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