Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001560332 | SCV001782721 | pathogenic | not provided | 2023-06-14 | criteria provided, single submitter | clinical testing | Previously reported, using alternative nomenclature of c.1672_1674delAAG; p.K558del, to segregate with Charcot-Marie-Tooth (CMT) disease and neutropenia in a large Belgian family (Zuchner et al, 2005; Claeys et al, 2009); A different missense substitution at this same position, K562E, reported as K558E using alternative nomenclature, has also been reported to segregate with CMT and neutropenia in an Australian family, leading the authors to conclude that alterations at this position are associated with both CMT and neutropenia (Zuchner et al., 2005); In-frame deletion of 1 amino acid in a non-repeat region predicted to critically alter the protein; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22091729, 22385972, 22451505, 22396310, 20227276, 25492887, 19502294, 15731758, 33684277, 28877744, 16227997) |
Invitae | RCV001869214 | SCV002135425 | pathogenic | Charcot-Marie-Tooth disease dominant intermediate B | 2023-07-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on DNM2 function (PMID: 22451505). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 637073). This variant is also known as p.Lys558del. This variant has been observed in individual(s) with clinical features of DNM2-related conditions (PMID: 15731758, 19502294, 28877744). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant, c.1684_1686del, results in the deletion of 1 amino acid(s) of the DNM2 protein (p.Lys562del), but otherwise preserves the integrity of the reading frame. |
Ambry Genetics | RCV002397560 | SCV002710689 | uncertain significance | Inborn genetic diseases | 2021-02-19 | criteria provided, single submitter | clinical testing | The c.1684_1686delAAG variant (also known as p.K562del) is located in coding exon 16 of the DNM2 gene. This variant results from an in-frame AAG deletion at nucleotide positions 1684 to 1686. This results in the in-frame deletion of a lysine at codon 562. This variant was found to segregate among multiple family members with Charcot-Marie-Tooth disease in one family (Züchner S et al. Nat Genet, 2005 Mar;37:289-94; Claeys KG et al. Brain, 2009 Jul;132:1741-52). Additionally, this variant was described as de novo in an individual with childhood-onset limb-girdle muscular dystrophy and elevated CK levels (Harris E et al. Orphanet J Rare Dis, 2017 09;12:151). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
OMIM | RCV002285173 | SCV000027902 | pathogenic | Charcot-Marie-Tooth disease, dominant intermediate B, with neutropenia | 2009-07-01 | no assertion criteria provided | literature only | |
Inherited Neuropathy Consortium | RCV000789092 | SCV000928443 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only | ||
Inherited Neuropathy Consortium Ii, |
RCV001869214 | SCV004174643 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate B | 2016-01-06 | no assertion criteria provided | literature only |