ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5065G>A (p.Ala1689Thr)

gnomAD frequency: 0.00001  dbSNP: rs767200163
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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 RCV001050538 SCV001214653 uncertain significance Hereditary breast ovarian cancer syndrome 2019-12-08 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is present in population databases (rs767200163, ExAC 0.002%). This sequence change replaces alanine with threonine at codon 1689 of the BRCA2 protein (p.Ala1689Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine.
Ambry Genetics RCV002339254 SCV002642764 uncertain significance Hereditary cancer-predisposing syndrome 2020-04-15 criteria provided, single submitter clinical testing The p.A1689T variant (also known as c.5065G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 5065. The alanine at codon 1689 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 RCV002339254 SCV003846968 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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