ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3325G>A (p.Ala1109Thr)

dbSNP: rs752886421
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000773764 SCV000907464 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV000773764 SCV001181414 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-13 criteria provided, single submitter clinical testing The p.A1109T variant (also known as c.3325G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 3325. The alanine at codon 1109 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002534095 SCV002961538 uncertain significance Hereditary breast ovarian cancer syndrome 2022-08-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1109 of the BRCA2 protein (p.Ala1109Thr). 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: 629076). 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000773764 SCV003851861 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 RCV003238810 SCV003936550 uncertain significance not provided 2022-12-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 3553G>A; This variant is associated with the following publications: (PMID: 29884841, 31911673, 32377563)

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