19-10718252-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001005361.3(DNM2):c.10C>T(p.Arg4Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000108 in 1,483,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152034Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000105 AC: 14AN: 1331016Hom.: 0 Cov.: 30 AF XY: 0.0000122 AC XY: 8AN XY: 656444
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152034Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74282
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease dominant intermediate B Uncertain:1
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 4 of the DNM2 protein (p.Arg4Cys). This variant is present in population databases (no rsID available, gnomAD 0.004%). 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: 859273). 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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at