ClinVar Miner

Submissions for variant NM_001005360.2(DNM2):c.1352G>A (p.Arg451Gln) (rs749154067)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236278 SCV000292770 uncertain significance not provided 2015-03-26 criteria provided, single submitter clinical testing The c.1352 G>A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Multiple in-silico splice prediction models predict that c.1352 G>A may create a cryptic splice acceptor site in exon 11 which may supplant the natural acceptor site and lead to abnormal splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. If c.1352 G>A does not alter splicing, it will result in the R451Q missense substitution, which is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in nearby residues have not been reported in the Human Gene Mutation Database in association with DNM2-related disorders (Stenson et al., 2014).

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.