rs606231133
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_173660.5(DOK7):βc.1378delβ(p.Gln460ArgfsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,596,906 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. A458A) has been classified as Likely benign.
Frequency
Consequence
NM_173660.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK7 | NM_173660.5 | c.1378del | p.Gln460ArgfsTer41 | frameshift_variant | 7/7 | ENST00000340083.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.1378del | p.Gln460ArgfsTer41 | frameshift_variant | 7/7 | 1 | NM_173660.5 | P1 | |
DOK7 | ENST00000643608.1 | c.946del | p.Gln316ArgfsTer78 | frameshift_variant | 5/8 | ||||
DOK7 | ENST00000515886.5 | c.448del | p.Gln150ArgfsTer41 | frameshift_variant | 4/4 | 2 | |||
DOK7 | ENST00000507039.5 | c.*599del | 3_prime_UTR_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000277 AC: 4AN: 1444696Hom.: 0 Cov.: 95 AF XY: 0.00000139 AC XY: 1AN XY: 717046
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | This sequence change creates a premature translational stop signal (p.Gln460Argfs*41) in the DOK7 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 45 amino acid(s) of the DOK7 protein. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DOK7-related conditions. This variant disrupts a region of the DOK7 protein in which other variant(s) (p.Pro486Argfs*15) have been determined to be pathogenic (PMID: 29118959). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Fetal akinesia deformation sequence 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 29, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at