ClinVar Miner

Submissions for variant NM_001005361.3(DNM2):c.1664_1671+1del

dbSNP: rs1568314339
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000689012 SCV000816647 uncertain significance Charcot-Marie-Tooth disease dominant intermediate B 2018-01-01 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. 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. 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). This variant has been reported in an individual affected with Charcot-Marie-Tooth disease (PMID: 15731758). This variant is not present in population databases (ExAC no frequency).
OMIM RCV000689012 SCV000027900 pathogenic Charcot-Marie-Tooth disease dominant intermediate B 2005-03-01 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000789091 SCV000928442 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Inherited Neuropathy Consortium Ii, University Of Miami RCV000689012 SCV004174770 uncertain significance Charcot-Marie-Tooth disease dominant intermediate B 2016-01-06 no assertion criteria provided literature only

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