ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9971C>A (p.Pro3324Gln)

dbSNP: rs1593202112
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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 RCV000795986 SCV000935471 uncertain significance Hereditary breast ovarian cancer syndrome 2024-02-05 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 3324 of the BRCA2 protein (p.Pro3324Gln). 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: 642508). 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.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001198192 SCV001369062 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2019-05-08 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3.
Ambry Genetics RCV002386398 SCV002694415 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-11 criteria provided, single submitter clinical testing The p.P3324Q variant (also known as c.9971C>A), located in coding exon 26 of the BRCA2 gene, results from a C to A substitution at nucleotide position 9971. The proline at codon 3324 is replaced by glutamine, 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.

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