Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000710123 | SCV000613147 | uncertain significance | not provided | 2017-06-08 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000710123 | SCV000621132 | uncertain significance | not provided | 2017-09-22 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DNM2 gene. The E457G variant has notbeen published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge.The E457G variant is not observed in large population cohorts (Lek et al., 2016). The E547G variantis a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, 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 and/or function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV002527468 | SCV003010444 | uncertain significance | Charcot-Marie-Tooth disease dominant intermediate B | 2023-01-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with DNM2-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNM2 protein function. ClinVar contains an entry for this variant (Variation ID: 447271). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 457 of the DNM2 protein (p.Glu457Gly). |
| Revvity Omics, |
RCV000710123 | SCV003830478 | uncertain significance | not provided | 2023-01-03 | criteria provided, single submitter | clinical testing |