rs746818628
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001005361.3(DNM2):c.2593G>A(p.Glu865Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,610,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E865Q) has been classified 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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM2 | NM_001005361.3 | c.2593G>A | p.Glu865Lys | missense_variant | 21/21 | ENST00000389253.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM2 | ENST00000389253.9 | c.2593G>A | p.Glu865Lys | missense_variant | 21/21 | 5 | NM_001005361.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151930Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000417 AC: 1AN: 239800Hom.: 0 AF XY: 0.00000766 AC XY: 1AN XY: 130540
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1458538Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 725296
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151930Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74202
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 28, 2021 | The p.E865K variant (also known as c.2593G>A), located in coding exon 21 of the DNM2 gene, results from a G to A substitution at nucleotide position 2593. The glutamic acid at codon 865 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2023 | ClinVar contains an entry for this variant (Variation ID: 585794). This variant has not been reported in the literature in individuals affected with DNM2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 865 of the DNM2 protein (p.Glu865Lys). 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
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 22, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at