rs9684786

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173660.5(DOK7):c.1382G>A(p.Gly461Asp) variant causes a missense change. The variant allele was found at a frequency of 0.203 in 1,595,910 control chromosomes in the GnomAD database, including 34,550 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G461G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.19 ( 2813 hom., cov: 34)

Exomes 𝑓: 0.20 ( 31737 hom. )

Consequence

DOK7
NM_173660.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.10

Publications

20 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056107044).

BP6

Variant 4-3493368-G-A is Benign according to our data. Variant chr4-3493368-G-A is described in ClinVar as Benign. ClinVar VariationId is 128911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK7	NM_173660.5 link	c.1382G>A	p.Gly461Asp	missense_variant	Exon 7 of 7	ENST00000340083.6	NP_775931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DOK7	ENST00000340083.6 link	c.1382G>A	p.Gly461Asp	missense_variant	Exon 7 of 7	1	NM_173660.5	ENSP00000344432.5
DOK7	ENST00000643608.1 link	c.950G>A	p.Gly317Asp	missense_variant	Exon 5 of 8			ENSP00000495701.1
DOK7	ENST00000515886.5 link	c.452G>A	p.Gly151Asp	missense_variant	Exon 4 of 4	2		ENSP00000492194.1
DOK7	ENST00000507039.5 link	c.*603G>A		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000423614.1

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28312

AN:

152132

Hom.:

2805

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.187

GnomAD2 exomes

AF:

0.207

AC:

42761

AN:

206948

AF XY:

0.213

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.211

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.156

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.205

AC:

295694

AN:

1443660

Hom.:

31737

Cov.:

AF XY:

0.209

AC XY:

149530

AN XY:

716614

show subpopulations

African (AFR)

AF:

0.145

AC:

4805

AN:

33170

American (AMR)

AF:

0.215

AC:

9036

AN:

42124

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

4448

AN:

25690

East Asian (EAS)

AF:

0.0912

AC:

3555

AN:

38996

South Asian (SAS)

AF:

0.319

AC:

26938

AN:

84458

European-Finnish (FIN)

AF:

0.150

AC:

7514

AN:

50220

Middle Eastern (MID)

AF:

0.164

AC:

933

AN:

5696

European-Non Finnish (NFE)

AF:

0.205

AC:

226746

AN:

1103756

Other (OTH)

AF:

0.197

AC:

11719

AN:

59550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

16061

32122

48183

64244

80305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7916

15832

23748

31664

39580

<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:

0.186

AC:

28335

AN:

152250

Hom.:

2813

Cov.:

AF XY:

0.189

AC XY:

14049

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.141

AC:

5880

AN:

41558

American (AMR)

AF:

0.228

AC:

3485

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

635

AN:

3470

East Asian (EAS)

AF:

0.124

AC:

644

AN:

5176

South Asian (SAS)

AF:

0.313

AC:

1508

AN:

4820

European-Finnish (FIN)

AF:

0.160

AC:

1697

AN:

10622

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13861

AN:

67982

Other (OTH)

AF:

0.186

AC:

394

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1204

2408

3612

4816

6020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.155

Hom.:

682

Bravo

AF:

0.185

TwinsUK

AF:

0.213

AC:

788

ALSPAC

AF:

0.200

AC:

770

ESP6500AA

AF:

0.116

AC:

491

ESP6500EA

AF:

0.184

AC:

1533

ExAC

AF:

0.189

AC:

22045

Asia WGS

AF:

0.182

AC:

631

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 28, 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. -

Feb 18, 2015

Eurofins Ntd Llc (ga)

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

- -

Fetal akinesia deformation sequence 1

Benign:1

May 28, 2019

Mendelics

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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.088

T;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.47

T;T;T

MetaRNN

Benign

0.0056

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

M;.;.

PhyloP100

4.1

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.6

D;.;.

REVEL

Benign

0.16

Sift

Benign

0.043

D;.;.

Sift4G

Uncertain

0.014

D;.;.

Polyphen

0.0050

B;.;.

Vest4

0.067

MPC

0.0045

ClinPred

0.020

GERP RS

2.6

Varity_R

0.16

gMVP

0.074

Mutation Taster

=95/5

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