ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.164C>T (p.Ala55Val)

gnomAD frequency: 0.00001  dbSNP: rs730881928
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000759333 SCV000211623 uncertain significance not provided 2023-07-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast cancer and in unaffected controls (Dorling et al., 2021); This variant is associated with the following publications: (PMID: 35624308, 33471991)
Ambry Genetics RCV000214683 SCV000278015 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-04 criteria provided, single submitter clinical testing The p.A55V variant (also known as c.164C>T), located in coding exon 2 of the RAD51C gene, results from a C to T substitution at nucleotide position 164. The alanine at codon 55 is replaced by valine, an amino acid with similar properties. This amino acid position is poorly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000648250 SCV000770064 uncertain significance Fanconi anemia complementation group O 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 55 of the RAD51C protein (p.Ala55Val). This variant is present in population databases (rs730881928, gnomAD 0.005%). This missense change has been observed in individual(s) with breast cancer (PMID: 28864920). ClinVar contains an entry for this variant (Variation ID: 182831). 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. Experimental studies have shown that this missense change does not substantially affect RAD51C function (PMID: 28864920). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759333 SCV000888593 uncertain significance not provided 2018-03-13 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000214683 SCV000909438 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-21 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 55 of the RAD51C protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been performed for this variant.This variant has been detected in a breast cancer case-control meta-analysis in 1/60466 cases and 3/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID RAD51C_000086). This variant has been identified in 4/282586 chromosomes 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.
Sema4, Sema4 RCV000214683 SCV002531801 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-01 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV002485003 SCV002788302 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O 2021-10-12 criteria provided, single submitter clinical testing

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