rs543344505
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_173660.5(DOK7):c.1470G>A(p.Ser490Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 1,610,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
DOK7
NM_173660.5 synonymous
NM_173660.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.606
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 Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 4-3493456-G-A is Benign according to our data. Variant chr4-3493456-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465678.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.606 with no splicing effect.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.1470G>A | p.Ser490Ser | synonymous_variant | Exon 7 of 7 | 1 | NM_173660.5 | ENSP00000344432.5 | ||
DOK7 | ENST00000643608.1 | c.1038G>A | p.Ser346Ser | synonymous_variant | Exon 5 of 8 | ENSP00000495701.1 | ||||
DOK7 | ENST00000515886.5 | c.540G>A | p.Ser180Ser | synonymous_variant | Exon 4 of 4 | 2 | ENSP00000492194.1 | |||
DOK7 | ENST00000507039.5 | c.*691G>A | 3_prime_UTR_variant | Exon 7 of 7 | 2 | ENSP00000423614.1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152218Hom.: 0 Cov.: 35
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GnomAD3 exomes AF: 0.0000935 AC: 22AN: 235338Hom.: 0 AF XY: 0.000100 AC XY: 13AN XY: 129700
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GnomAD4 exome AF: 0.0000254 AC: 37AN: 1457746Hom.: 0 Cov.: 87 AF XY: 0.0000234 AC XY: 17AN XY: 724966
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152336Hom.: 0 Cov.: 35 AF XY: 0.0000671 AC XY: 5AN XY: 74490
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10 Benign:1
Jan 29, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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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