ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.31T>C (p.Phe11Leu)

dbSNP: rs1566214589
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Sema4, Sema4 RCV002258464 SCV002533771 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-14 criteria provided, single submitter curation
Ambry Genetics RCV002258464 SCV002609149 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-09 criteria provided, single submitter clinical testing The p.F11L variant (also known as c.31T>C), located in coding exon 1 of the BRCA2 gene, results from a T to C substitution at nucleotide position 31. The phenylalanine at codon 11 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is 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.
Color Diagnostics, LLC DBA Color Health RCV002258464 SCV004361148 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-28 criteria provided, single submitter clinical testing This missense variant replaces phenylalanine with leucine at codon 11 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least one individual affected with breast cancer (PMID: 33113089). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003645243 SCV004425721 uncertain significance Hereditary breast ovarian cancer syndrome 2023-12-26 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 11 of the BRCA2 protein (p.Phe11Leu). 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: 1692109). 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.

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