rs138128705
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_001005361.3(DNM2):c.811C>T(p.Arg271Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,124 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R271H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001005361.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM2 | NM_001005361.3 | c.811C>T | p.Arg271Cys | missense_variant | 6/21 | ENST00000389253.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM2 | ENST00000389253.9 | c.811C>T | p.Arg271Cys | missense_variant | 6/21 | 5 | NM_001005361.3 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249900Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135236
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461124Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 726860
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease dominant intermediate B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2019 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DNM2-related disease. This variant is present in population databases (rs138128705, ExAC 0.003%). This sequence change replaces arginine with cysteine at codon 271 of the DNM2 protein (p.Arg271Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at