rs191800156
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 GnomAd at 23 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK7 | NM_173660.5 | c.-6C>G | 5_prime_UTR_variant | 1/7 | ENST00000340083.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.-6C>G | 5_prime_UTR_variant | 1/7 | 1 | NM_173660.5 | P1 |
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:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 24, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 11, 2016 | - - |
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. - |
DOK7-related disorder Benign:1
Benign, criteria provided, single submitter | 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
Benign
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