rs6811856

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173660.5(DOK7):c.1113A>C(p.Ser371Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,579,746 control chromosomes in the GnomAD database, including 40,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3574 hom., cov: 34)

Exomes 𝑓: 0.22 ( 36706 hom. )

Consequence

DOK7
NM_173660.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.44

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 4-3493099-A-C is Benign according to our data. Variant chr4-3493099-A-C is described in ClinVar as [Benign]. Clinvar id is 128904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3493099-A-C is described in Lovd as [Benign]. Variant chr4-3493099-A-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK7	NM_173660.5 link	c.1113A>C	p.Ser371Ser	synonymous_variant	Exon 7 of 7	ENST00000340083.6	NP_775931.3	Q18PE1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6 link	c.1113A>C	p.Ser371Ser	synonymous_variant	Exon 7 of 7	1	NM_173660.5	ENSP00000344432.5		Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28587

AN:

152040

Hom.:

3579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0557

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.191

GnomAD3 exomes

AF:

0.224

AC:

42420

AN:

189222

Hom.:

5618

AF XY:

0.227

AC XY:

23580

AN XY:

104016

show subpopulations

Gnomad AFR exome

AF:

0.0524

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.489

Gnomad SAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.380

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.217

AC:

309943

AN:

1427588

Hom.:

36706

Cov.:

110

AF XY:

0.217

AC XY:

154015

AN XY:

708228

show subpopulations

Gnomad4 AFR exome

AF:

0.0481

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.222

Gnomad4 EAS exome

AF:

0.507

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.188

AC:

28585

AN:

152158

Hom.:

3574

Cov.:

AF XY:

0.195

AC XY:

14505

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0556

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.211

Gnomad4 EAS

AF:

0.514

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.216

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.193

Hom.:

2595

Bravo

AF:

0.166

Asia WGS

AF:

0.366

AC:

1273

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Nov 21, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 05, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.38

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over