ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8999T>C (p.Leu3000Ser)

dbSNP: rs80359151
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001914673 SCV002141783 uncertain significance Hereditary breast ovarian cancer syndrome 2023-09-05 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA2 protein function. This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 3000 of the BRCA2 protein (p.Leu3000Ser). 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: 1378709).
Ambry Genetics RCV003355606 SCV004052646 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-13 criteria provided, single submitter clinical testing The p.L3000S variant (also known as c.8999T>C), located in coding exon 22 of the BRCA2 gene, results from a T to C substitution at nucleotide position 8999. The leucine at codon 3000 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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