ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.758A>G (p.Asp253Gly) (rs1060502592)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566748 SCV000667102 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Insufficient or conflicting evidence
Color RCV000566748 SCV000686385 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-08 criteria provided, single submitter clinical testing
GeneDx RCV000481758 SCV000569624 uncertain significance not provided 2017-10-20 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.758A>G at the cDNA level, p.Asp253Gly (D253G) at the protein level, and results in the change of an Aspartic Acid to a Glycine (GAT>GGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C Asp253Gly was not observed in large population cohorts (Lek 2016). Since Aspartic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. RAD51C Asp253Gly occurs at a position where amino acids with properties similar to Aspartic Acid are tolerated across species and is located within the region interaction with RAD51B, RAD51D, and XRCC3 (Miller 2004). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether RAD51C Asp253Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000460712 SCV000550209 uncertain significance Fanconi anemia, complementation group O 2018-09-10 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 253 of the RAD51C protein (p.Asp253Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 28202063). ClinVar contains an entry for this variant (Variation ID: 409850). 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: "Deleterious"; PolyPhen-2: "Benign"; 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.

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.