rs6831659

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.1134G>A(p.Ala378Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,590,450 control chromosomes in the GnomAD database, including 38,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A378A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.18 ( 3380 hom., cov: 34)

Exomes 𝑓: 0.21 ( 34931 hom. )

Consequence

DOK7
NM_173660.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.09

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 4-3493120-G-A is Benign according to our data. Variant chr4-3493120-G-A is described in ClinVar as Benign. ClinVar VariationId is 128905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK7	NM_173660.5 link	c.1134G>A	p.Ala378Ala	synonymous_variant	Exon 7 of 7	ENST00000340083.6	NP_775931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6 link	c.1134G>A	p.Ala378Ala	synonymous_variant	Exon 7 of 7	1	NM_173660.5	ENSP00000344432.5

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27667

AN:

152054

Hom.:

3385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.222

AC:

45117

AN:

203522

AF XY:

0.224

show subpopulations

Gnomad AFR exome

AF:

0.0533

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.490

Gnomad FIN exome

AF:

0.378

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.210

AC:

302498

AN:

1438278

Hom.:

34931

Cov.:

113

AF XY:

0.211

AC XY:

150616

AN XY:

714238

show subpopulations

African (AFR)

AF:

0.0469

AC:

1553

AN:

33108

American (AMR)

AF:

0.140

AC:

5887

AN:

42022

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

5436

AN:

25746

East Asian (EAS)

AF:

0.505

AC:

19382

AN:

38370

South Asian (SAS)

AF:

0.206

AC:

17290

AN:

83772

European-Finnish (FIN)

AF:

0.378

AC:

17590

AN:

46524

Middle Eastern (MID)

AF:

0.147

AC:

845

AN:

5744

European-Non Finnish (NFE)

AF:

0.201

AC:

222005

AN:

1103496

Other (OTH)

AF:

0.210

AC:

12510

AN:

59496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

17651

35303

52954

70606

88257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7744

15488

23232

30976

38720

<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:

0.182

AC:

27665

AN:

152172

Hom.:

3380

Cov.:

AF XY:

0.189

AC XY:

14091

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0538

AC:

2236

AN:

41564

American (AMR)

AF:

0.146

AC:

2237

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

690

AN:

3470

East Asian (EAS)

AF:

0.511

AC:

2630

AN:

5146

South Asian (SAS)

AF:

0.223

AC:

1079

AN:

4828

European-Finnish (FIN)

AF:

0.380

AC:

4027

AN:

10584

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14065

AN:

67960

Other (OTH)

AF:

0.186

AC:

392

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1106

2213

3319

4426

5532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.165

Hom.:

1080

Bravo

AF:

0.160

Asia WGS

AF:

0.363

AC:

1266

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 23, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

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

- -

Feb 19, 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. -

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

-0.84

CADD

Benign

0.27

(source)

DANN

Benign

0.77

PhyloP100

-1.1

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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