ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.154A>C (p.Ile52Leu)

gnomAD frequency: 0.00001  dbSNP: rs730881927
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160918 SCV000211622 uncertain significance not provided 2024-02-20 criteria provided, single submitter clinical testing Observed in 1 out of 427 cancer-free control subjects but was not found among 1,655 women with a personal history of breast and/or ovarian cancer (PMID: 21990120); In silico analysis supports that this missense variant does not alter protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21990120)
Labcorp Genetics (formerly Invitae), Labcorp RCV000198840 SCV000255186 uncertain significance Fanconi anemia complementation group O 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 52 of the RAD51C protein (p.Ile52Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 182830). 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 RAD51C protein function with a negative predictive value of 80%. 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 RCV000563190 SCV000667110 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-10 criteria provided, single submitter clinical testing The p.I52L variant (also known as c.154A>C), located in coding exon 2 of the RAD51C gene, results from an A to C substitution at nucleotide position 154. The isoleucine at codon 52 is replaced by leucine, an amino acid with highly similar properties. This variant was previously detected in 0/1388 hereditary breast and/or ovarian cancer families and 1/427 controls (Thompson et al. Hum. Mutat. 2012; 33: 95-9). 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 RCV000563190 SCV000906586 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-06 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with leucine at codon 52 of the RAD51C 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 not been reported in individuals affected with hereditary cancer in the literature and has been observed in one unaffected control individual (PMID: 21990120). 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.
Baylor Genetics RCV003462104 SCV004207920 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3 2024-03-21 criteria provided, single submitter clinical testing
Leiden Open Variation Database RCV001195011 SCV001365246 likely benign not specified 2011-08-25 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Ian Campbell.

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