ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.875G>A (p.Arg292Gln)

gnomAD frequency: 0.00001  dbSNP: rs747060782
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000204197 SCV000259693 uncertain significance Fanconi anemia 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 292 of the FANCC protein (p.Arg292Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs747060782, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 219684). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV000214971 SCV000278973 uncertain significance not provided 2024-01-16 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; Observed in an individual with breast cancer (PMID: 26689913); This variant is associated with the following publications: (PMID: Gordon2000[Book], 26689913)
Ambry Genetics RCV001018284 SCV001179500 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-09 criteria provided, single submitter clinical testing The p.R292Q variant (also known as c.875G>A), located in coding exon 8 of the FANCC gene, results from a G to A substitution at nucleotide position 875. The arginine at codon 292 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in an individual diagnosed with breast cancer from a cohort of 4034 cancer cases from The Cancer Genome Atlas (Lu C et al. Nat Commun, 2015 Dec;6:10086). This amino acid position is highly 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.
Fulgent Genetics, Fulgent Genetics RCV002485337 SCV002793249 uncertain significance Fanconi anemia complementation group C 2021-11-09 criteria provided, single submitter clinical testing
Natera, Inc. RCV000204197 SCV002081211 uncertain significance Fanconi anemia 2018-09-03 no assertion criteria provided clinical testing

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