rs9684786
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_173660.5(DOK7):c.1382G>A(p.Gly461Asp) variant causes a missense change. The variant allele was found at a frequency of 0.203 in 1,595,910 control chromosomes in the GnomAD database, including 34,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.19 ( 2813 hom., cov: 34)
Exomes 𝑓: 0.20 ( 31737 hom. )
Consequence
DOK7
NM_173660.5 missense
NM_173660.5 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 4.10
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0056107044).
BP6
?
Variant 4-3493368-G-A is Benign according to our data. Variant chr4-3493368-G-A is described in ClinVar as [Benign]. Clinvar id is 128911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3493368-G-A is described in Lovd as [Benign]. Variant chr4-3493368-G-A is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK7 | NM_173660.5 | c.1382G>A | p.Gly461Asp | missense_variant | 7/7 | ENST00000340083.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.1382G>A | p.Gly461Asp | missense_variant | 7/7 | 1 | NM_173660.5 | P1 | |
DOK7 | ENST00000643608.1 | c.950G>A | p.Gly317Asp | missense_variant | 5/8 | ||||
DOK7 | ENST00000515886.5 | c.452G>A | p.Gly151Asp | missense_variant | 4/4 | 2 | |||
DOK7 | ENST00000507039.5 | c.*603G>A | 3_prime_UTR_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.186 AC: 28312AN: 152132Hom.: 2805 Cov.: 34
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GnomAD3 exomes AF: 0.207 AC: 42761AN: 206948Hom.: 4684 AF XY: 0.213 AC XY: 24332AN XY: 114376
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GnomAD4 exome AF: 0.205 AC: 295694AN: 1443660Hom.: 31737 Cov.: 95 AF XY: 0.209 AC XY: 149530AN XY: 716614
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GnomAD4 genome ? AF: 0.186 AC: 28335AN: 152250Hom.: 2813 Cov.: 34 AF XY: 0.189 AC XY: 14049AN XY: 74448
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788
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770
ESP6500AA
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491
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1533
ExAC
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22045
Asia WGS
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631
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 18, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 28, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 15, 2013 | - - |
Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Fetal akinesia deformation sequence 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.;.
MutationTaster
Benign
P;P;P
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.
REVEL
Benign
Sift
Benign
D;.;.
Sift4G
Uncertain
D;.;.
Polyphen
B;.;.
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at