ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3424T>C (p.Phe1142Leu)

dbSNP: rs2072480095
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001227125 SCV001399466 uncertain significance Hereditary breast ovarian cancer syndrome 2019-09-09 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 1142 of the BRCA2 protein (p.Phe1142Leu). The phenylalanine residue is weakly conserved and there is a small physicochemical difference between phenylalanine and leucine.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158558 SCV003851950 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 RCV003158558 SCV004915394 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-28 criteria provided, single submitter clinical testing The c.3424T>C (p.F1142L) alteration is located in exon 11 (coding exon 10) of the BRCA2 gene. This alteration results from a T to C substitution at nucleotide position 3424, causing the phenylalanine (F) at amino acid position 1142 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004783929 SCV005396357 uncertain significance not provided 2024-05-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 3652T>C

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