ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9898C>A (p.Pro3300Thr)

gnomAD frequency: 0.00001  dbSNP: rs770868371
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215835 SCV000274715 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-23 criteria provided, single submitter clinical testing The p.P3300T variant (also known as c.9898C>A), located in coding exon 26 of the BRCA2 gene, results from a C to A substitution at nucleotide position 9898. The proline at codon 3300 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is highly 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.
Color Diagnostics, LLC DBA Color Health RCV000215835 SCV000684099 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001044013 SCV001207786 uncertain significance Hereditary breast ovarian cancer syndrome 2024-10-15 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 3300 of the BRCA2 protein (p.Pro3300Thr). This variant is present in population databases (rs770868371, gnomAD 0.007%). 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: 230995). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004998453 SCV005625361 uncertain significance not provided 2024-03-08 criteria provided, single submitter clinical testing The BRCA2 c.9898C>A (p.Pro3300Thr) variant has not been reported in individuals with BRCA2-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/251222 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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