rs118203995
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2
The NM_173660.5(DOK7):c.601C>G(p.Arg201Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R201Q) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 34)
Consequence
DOK7
NM_173660.5 missense
NM_173660.5 missense
Scores
3
6
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.37
Publications
7 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
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM1
In a domain IRS-type PTB (size 105) in uniprot entity DOK7_HUMAN there are 11 pathogenic changes around while only 2 benign (85%) in NM_173660.5
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD2 exomes AF: 0.00000408 AC: 1AN: 245210 AF XY: 0.00000751 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
245210
AF XY:
Gnomad AFR exome
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Gnomad EAS exome
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Gnomad FIN exome
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GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
GnomAD4 genome
Cov.:
34
ExAC
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T
MetaSVM
Uncertain
D
PhyloP100
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Gain of MoRF binding (P = 0.0049);
MVP
ClinPred
D
GERP RS
Varity_R
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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