ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.875G>A (p.Arg292Gln) (rs747060782)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204197 SCV000259693 uncertain significance Fanconi anemia 2018-05-02 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 with FANCC-related disease. ClinVar contains an entry for this variant (Variation ID: 219684). Algorithms developed to predict the effect of missense changes on protein structure and function 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, but this prediction has not been confirmed by published transcriptional studies. 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 2018-10-29 criteria provided, single submitter clinical testing This variant is denoted FANCC c.875G>A at the cDNA level, p.Arg292Gln (R292Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has been observed in at least one individual with breast cancer (Lu 2015). FANCC Arg292Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the region that interacts with Hsp70 and GRP94 (Gordon 2000). Protein-based in silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. In addition, multiple splicing models predict the creation of a novel splice site. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. Based on currently available evidence, it is unclear whether FANCC Arg292Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.