Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000466061 | SCV000549955 | uncertain significance | Fanconi anemia | 2022-03-05 | criteria provided, single submitter | clinical testing | This sequence change affects codon 174 of the FANCC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the FANCC protein. This variant also falls at the last nucleotide of exon 6, which is part of the consensus splice site for this exon. This variant is present in population databases (rs755283850, gnomAD 0.006%). 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: 409653). 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 glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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. |
| Ambry Genetics | RCV001023751 | SCV001185669 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-12 | criteria provided, single submitter | clinical testing | The p.R174Q variant (also known as c.521G>A), located in coding exon 5 of the FANCC gene, results from a G to A substitution at nucleotide position 521. The amino acid change results in arginine to glutamine at codon 174, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 5, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). This amino acid position is well conserved in available vertebrate species. In addition, as a missense substitution this 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. |
| Gene |
RCV002244938 | SCV002513178 | uncertain significance | not provided | 2024-06-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Gordon2000[Book]) |
| Fulgent Genetics, |
RCV002481439 | SCV002784181 | uncertain significance | Fanconi anemia complementation group C | 2022-05-24 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000466061 | SCV002081259 | uncertain significance | Fanconi anemia | 2018-07-24 | no assertion criteria provided | clinical testing |