19-10718247-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP2PP3
The NM_001005361.3(DNM2):c.5G>A(p.Gly2Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000216 in 1,479,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001005361.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151984Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000218 AC: 29AN: 1327794Hom.: 0 Cov.: 31 AF XY: 0.0000183 AC XY: 12AN XY: 654698
GnomAD4 genome AF: 0.0000197 AC: 3AN: 151984Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74250
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The p.G2D variant (also known as c.5G>A), located in coding exon 1 of the DNM2 gene, results from a G to A substitution at nucleotide position 5. The glycine at codon 2 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Charcot-Marie-Tooth disease dominant intermediate B Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2 of the DNM2 protein (p.Gly2Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DNM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 835727). 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. 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. -
not provided Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 16227997) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at