ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.135G>C (p.Glu45Asp) (rs371608994)

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 RCV000564011 SCV000667130 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
GeneDx RCV000236631 SCV000293601 uncertain significance not provided 2017-09-01 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.135G>C at the cDNA level, p.Glu45Asp (E45D) at the protein level, and results in the change of a Glutamic Acid to an Aspartic Acid (GAG>GAC). This variant has not, to our knowledge, been published in the literature as a germline variant; however, it has been reported as a somatic variant in cholangiocarcinoma (Jiao 2013). RAD51C Glu45Asp was not observed at a significant allele frequency in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Glutamic Acid and Aspartic Acid share similar properties, this is considered a conservative amino acid substitution. RAD51C Glu45Asp occurs at a position that is not conserved and is located in a region required for Holliday junction resolution activity (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether RAD51C Glu45Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000553107 SCV000650006 uncertain significance Fanconi anemia, complementation group O 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 45 of the RAD51C protein (p.Glu45Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs371608994, ExAC 0.01%). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 246164). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236631 SCV000889815 uncertain significance not provided 2018-01-04 criteria provided, single submitter clinical testing

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.