rs377554325
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_173660.5(DOK7):c.308G>A(p.Arg103Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,594,576 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 (★★). Synonymous variant affecting the same amino acid position (i.e. R103R) has been classified as Likely benign.
Frequency
Consequence
NM_173660.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.308G>A | p.Arg103Gln | missense_variant | 3/7 | ENST00000340083.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.308G>A | p.Arg103Gln | missense_variant | 3/7 | 1 | NM_173660.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152254Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000314 AC: 7AN: 222970Hom.: 0 AF XY: 0.0000245 AC XY: 3AN XY: 122236
GnomAD4 exome AF: 0.0000139 AC: 20AN: 1442322Hom.: 0 Cov.: 34 AF XY: 0.0000126 AC XY: 9AN XY: 715242
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152254Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74380
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 21, 2017 | - - |
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 arginine with glutamine at codon 103 of the DOK7 protein (p.Arg103Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs377554325, ExAC 0.05%). This missense change has been observed in individual(s) with clinical features of DOK7-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 548006). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | Revvity Omics, Revvity | Dec 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at