ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3610G>A (p.Ala1204Thr)

dbSNP: rs1555283309
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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 RCV001206670 SCV001377990 uncertain significance Hereditary breast ovarian cancer syndrome 2019-09-25 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 1204 of the BRCA2 protein (p.Ala1204Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine.
Ambry Genetics RCV002451440 SCV002617457 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-03 criteria provided, single submitter clinical testing The p.A1204T variant (also known as c.3610G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 3610. The alanine at codon 1204 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly 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 RCV002451440 SCV003846735 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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