rs191800156
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_173660.5(DOK7):c.-6C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 1,487,404 control chromosomes in the GnomAD database, including 527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 23 hom., cov: 31)
Exomes 𝑓: 0.025 ( 504 hom. )
Consequence
DOK7
NM_173660.5 5_prime_UTR
NM_173660.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.69
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 -18 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
Variant 4-3463370-C-G is Benign according to our data. Variant chr4-3463370-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 193509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3463370-C-G is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0175 (2626/149922) while in subpopulation NFE AF= 0.0268 (1813/67748). AF 95% confidence interval is 0.0257. There are 23 homozygotes in gnomad4. There are 1197 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 23 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DOK7 | NM_173660.5 | c.-6C>G | 5_prime_UTR_variant | 1/7 | ENST00000340083.6 | NP_775931.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083 | c.-6C>G | 5_prime_UTR_variant | 1/7 | 1 | NM_173660.5 | ENSP00000344432.5 |
Frequencies
GnomAD3 genomes AF: 0.0175 AC: 2625AN: 149822Hom.: 23 Cov.: 31
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GnomAD3 exomes AF: 0.0149 AC: 1799AN: 121120Hom.: 21 AF XY: 0.0148 AC XY: 1020AN XY: 69074
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GnomAD4 exome AF: 0.0253 AC: 33901AN: 1337482Hom.: 504 Cov.: 33 AF XY: 0.0250 AC XY: 16523AN XY: 662094
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GnomAD4 genome AF: 0.0175 AC: 2626AN: 149922Hom.: 23 Cov.: 31 AF XY: 0.0164 AC XY: 1197AN XY: 73052
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 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 | Eurofins Ntd Llc (ga) | May 11, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 24, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
DOK7-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 26, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
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