rs754105518
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_173660.5(DOK7):āc.857A>Gā(p.Glu286Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000397 in 1,612,014 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E286K) has been classified as Uncertain significance.
Frequency
Consequence
NM_173660.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK7 | NM_173660.5 | c.857A>G | p.Glu286Gly | missense_variant | 7/7 | ENST00000340083.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.857A>G | p.Glu286Gly | missense_variant | 7/7 | 1 | NM_173660.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152174Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000244 AC: 6AN: 246362Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134014
GnomAD4 exome AF: 0.0000411 AC: 60AN: 1459840Hom.: 0 Cov.: 98 AF XY: 0.0000441 AC XY: 32AN XY: 726216
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152174Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74326
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 10;C4760599:Fetal akinesia deformation sequence 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 15, 2021 | - - |
Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 286 of the DOK7 protein (p.Glu286Gly). This variant is present in population databases (rs754105518, gnomAD 0.005%). 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: 465690). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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