ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9135A>T (p.Leu3045Phe)

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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 RCV003021258 SCV003312245 uncertain significance Hereditary breast ovarian cancer syndrome 2022-05-28 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 3045 of the BRCA2 protein (p.Leu3045Phe). 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. 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV003308423 SCV004005412 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-31 criteria provided, single submitter clinical testing The p.L3045F variant (also known as c.9135A>T), located in coding exon 23 of the BRCA2 gene, results from an A to T substitution at nucleotide position 9135. The leucine at codon 3045 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Baylor Genetics RCV003475466 SCV004212886 uncertain significance Familial cancer of breast 2021-11-05 criteria provided, single submitter clinical testing

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