ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.922T>C (p.Phe308Leu)

dbSNP: rs921111470
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001283948 SCV001469467 uncertain significance not provided 2019-09-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001871651 SCV002281519 uncertain significance Hereditary breast ovarian cancer syndrome 2023-02-22 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. 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) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. ClinVar contains an entry for this variant (Variation ID: 993054). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 308 of the BRCA2 protein (p.Phe308Leu).
University of Washington Department of Laboratory Medicine, University of Washington RCV003158639 SCV003848140 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics RCV003158639 SCV005102049 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-15 criteria provided, single submitter clinical testing The p.F308L variant (also known as c.922T>C), located in coding exon 9 of the BRCA2 gene, results from a T to C substitution at nucleotide position 922. The phenylalanine at codon 308 is replaced by leucine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with breast cancer (Ren M et al. Breast Cancer Res Treat, 2021 Sep;189:533-539). 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. Based on the available evidence, the clinical significance of this alteration remains unclear.

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