ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.34C>T (p.Arg12Trp)

gnomAD frequency: 0.00004  dbSNP: rs28910276
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000464422 SCV000550187 uncertain significance Fanconi anemia complementation group O 2024-01-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 12 of the RAD51C protein (p.Arg12Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with breast cancer (PMID: 21537932). ClinVar contains an entry for this variant (Variation ID: 409837). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
GeneDx RCV000485483 SCV000567112 uncertain significance not provided 2024-01-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies are inconclusive: moderately deficient homologous recombination activity and impaired protein-protein interactions (PMID: 36099300); This variant is associated with the following publications: (PMID: 24631219, 21537932, 36099300)
Ambry Genetics RCV000574346 SCV000671901 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-23 criteria provided, single submitter clinical testing The p.R12W variant (also known as c.34C>T), located in coding exon 1 of the RAD51C gene, results from a C to T substitution at nucleotide position 34. The arginine at codon 12 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000574346 SCV000686345 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-24 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001526803 SCV001737435 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3 2021-06-10 criteria provided, single submitter clinical testing The RAD51C c.34C>T (p.Arg12Trp) missense change has a maximum subpopulation frequency of 0.0080% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/17-56770038-C-T?dataset=gnomad_r2_1). In silico tools are not in agreement about the effect of this variant on protein function, but to our knowledge these predictions have not been confirmed by functional assays. This variant is present 2X in the FLOSSIES database which contains genetic variants from women older than 70 years of age who have never had cancer (BS2_Supporting; https://whi.color.com/variant/17-56770038-C-T). This variant was investigated in a case control study of 81 patients with head and neck cancer and 156 healthy control individuals (PMID: 24631219) and a study of 132 breast cancer cases and 189 healthy control individuals (PMID: 31905201), however it was not observed in any cases or controls. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BS2_Supporting.
Sema4, Sema4 RCV000574346 SCV002531810 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-07 criteria provided, single submitter curation
Baylor Genetics RCV001526803 SCV004207958 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3 2023-11-18 criteria provided, single submitter clinical testing

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