rs767909551
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173660.5(DOK7):c.1403G>A(p.Gly468Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000658 in 1,594,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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. G468C) has been classified as Uncertain significance.
Frequency
Consequence
NM_173660.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK7 | NM_173660.5 | c.1403G>A | p.Gly468Asp | missense_variant | 7/7 | ENST00000340083.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.1403G>A | p.Gly468Asp | missense_variant | 7/7 | 1 | NM_173660.5 | P1 | |
DOK7 | ENST00000643608.1 | c.971G>A | p.Gly324Asp | missense_variant | 5/8 | ||||
DOK7 | ENST00000515886.5 | c.473G>A | p.Gly158Asp | missense_variant | 4/4 | 2 | |||
DOK7 | ENST00000507039.5 | c.*624G>A | 3_prime_UTR_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152198Hom.: 0 Cov.: 35
GnomAD3 exomes AF: 0.0000644 AC: 13AN: 201980Hom.: 0 AF XY: 0.0000896 AC XY: 10AN XY: 111614
GnomAD4 exome AF: 0.0000645 AC: 93AN: 1442532Hom.: 0 Cov.: 88 AF XY: 0.0000628 AC XY: 45AN XY: 716168
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152198Hom.: 0 Cov.: 35 AF XY: 0.0000941 AC XY: 7AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 25, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 06, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces glycine with aspartic acid at codon 468 of the DOK7 protein (p.Gly468Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs767909551, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with DOK7-related conditions. ClinVar contains an entry for this variant (Variation ID: 465677). 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 tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at