ClinVar Miner

Submissions for variant NM_004945.3(DNM2):c.1652_1659+1del (rs1568314339)

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 RCV000689012 SCV000816647 uncertain significance Charcot-Marie-Tooth disease, dominant intermediate B 2018-01-15 criteria provided, single submitter clinical testing This sequence change removes the last 8 nucleotides of exon 8 and the first nucleotide of intron 9, affecting a donor splice site in intron 9 of the DNM2 gene. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Charcot-Marie-Tooth disease (PMID: 15731758). Experimental studies have shown that this change results in two abnormally spliced mRNA transcripts from the DNM2 gene, resulting in a protein with a premature truncation, p.Asp555Valfs*35 (also known as K550fs), or an in-frame deletion, p.Asp555_Glu557del (PMID: 15731758). p.Asp555_Glu557del is also known as 555delta3 or D551_E553del in the literature. Lysates from affected individuals with this variant did not show a reduced level of protein, suggesting that nonsense-mediated decay was not activated (PMID: 15731758). However, experiments show that protein containing p.Asp555_Glu557del is defective in microtubule organization, formation and endocytosis (PMID: 15731758, 21762456, 27328317). 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.
Inherited Neuropathy Consortium RCV000789091 SCV000928442 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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.