rs377757018
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_173660.5(DOK7):c.1007C>A(p.Ser336*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S336S) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DOK7
NM_173660.5 stop_gained
NM_173660.5 stop_gained
Scores
2
2
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.62
Publications
0 publications found
Genes affected
DOK7 (HGNC:26594): (docking protein 7) The protein encoded by this gene is essential for neuromuscular synaptogenesis. The protein functions in aneural activation of muscle-specific receptor kinase, which is required for postsynaptic differentiation, and in the subsequent clustering of the acetylcholine receptor in myotubes. This protein can also induce autophosphorylation of muscle-specific receptor kinase. Mutations in this gene are a cause of familial limb-girdle myasthenia autosomal recessive, which is also known as congenital myasthenic syndrome type 1B. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
DOK7 Gene-Disease associations (from GenCC):
- congenital myasthenic syndrome 10Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
- fetal akinesia deformation sequence 3Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- fetal akinesia deformation sequence 1Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- postsynaptic congenital myasthenic syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 55 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1406180Hom.: 0 Cov.: 112 AF XY: 0.00 AC XY: 0AN XY: 695914
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1406180
Hom.:
Cov.:
112
AF XY:
AC XY:
0
AN XY:
695914
African (AFR)
AF:
AC:
0
AN:
32572
American (AMR)
AF:
AC:
0
AN:
37620
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25312
East Asian (EAS)
AF:
AC:
0
AN:
37078
South Asian (SAS)
AF:
AC:
0
AN:
81096
European-Finnish (FIN)
AF:
AC:
0
AN:
40040
Middle Eastern (MID)
AF:
AC:
0
AN:
5718
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1088218
Other (OTH)
AF:
AC:
0
AN:
58526
GnomAD4 genome
GnomAD4 genome
Cov.:
34
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
PhyloP100
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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