rs6811856

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 10
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
fetal akinesia deformation sequence 3
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
fetal akinesia deformation sequence 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DOK7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 128904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

GnomAD2 exomes

AF:

0.224

AC:

42420

AN:

189222

AF XY:

0.227

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 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

African (AFR)

AF:

0.0481

AC:

1584

AN:

32950

American (AMR)

AF:

0.143

AC:

5810

AN:

40532

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

5676

AN:

25624

East Asian (EAS)

AF:

0.507

AC:

19129

AN:

37738

South Asian (SAS)

AF:

0.209

AC:

17299

AN:

82722

European-Finnish (FIN)

AF:

0.381

AC:

16812

AN:

44122

Middle Eastern (MID)

AF:

0.148

AC:

850

AN:

5742

European-Non Finnish (NFE)

AF:

0.209

AC:

229974

AN:

1098934

Other (OTH)

AF:

0.216

AC:

12809

AN:

59224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

18630

37260

55890

74520

93150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7984

15968

23952

31936

39920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.188

AC:

28585

AN:

152158

Hom.:

3574

Cov.:

AF XY:

0.195

AC XY:

14505

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0556

AC:

2310

AN:

41546

American (AMR)

AF:

0.152

AC:

2330

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

731

AN:

3470

East Asian (EAS)

AF:

0.514

AC:

2649

AN:

5158

South Asian (SAS)

AF:

0.226

AC:

1091

AN:

4830

European-Finnish (FIN)

AF:

0.385

AC:

4073

AN:

10570

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14692

AN:

67970

Other (OTH)

AF:

0.191

AC:

402

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1154

2309

3463

4618

5772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.190

Hom.:

2900

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

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. -

Nov 21, 2014

Eurofins Ntd Llc (ga)

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

(source)

DANN

Benign

0.59

PhyloP100

-4.4

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over