ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3610G>T (p.Ala1204Ser)

dbSNP: rs1555283309
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000637609 SCV000759075 uncertain significance Hereditary breast ovarian cancer syndrome 2024-02-29 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1204 of the BRCA2 protein (p.Ala1204Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 531348). 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 with a negative predictive value of 95%. 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.
Ambry Genetics RCV002458024 SCV002616662 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-28 criteria provided, single submitter clinical testing The p.A1204S variant (also known as c.3610G>T), located in coding exon 10 of the BRCA2 gene, results from a G to T substitution at nucleotide position 3610. The alanine at codon 1204 is replaced by serine, 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.
Revvity Omics, Revvity RCV003144409 SCV003830159 uncertain significance not provided 2022-04-11 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV002458024 SCV003846734 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).
GeneDx RCV003144409 SCV005325312 uncertain significance not provided 2023-12-31 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 3838G>T

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