Total submissions: 2
| 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 |