rs9684786

Positions:

Variant summary

Our verdict is Benign. Variant got -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. Variant has been reported in ClinVar as 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

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 -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 id is 128911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3493368-G-A is described in Lovd as [Benign]. Variant chr4-3493368-G-A is described in Lovd as [Likely_benign].

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/exons	MANE	UniProt
DOK7	NM_173660.5 linkuse as main transcript	c.1382G>A	p.Gly461Asp	missense_variant	7/7	ENST00000340083.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK7	ENST00000340083.6 linkuse as main transcript	c.1382G>A	p.Gly461Asp	missense_variant	7/7	1	NM_173660.5	P1	Q18PE1-1
DOK7	ENST00000643608.1 linkuse as main transcript	c.950G>A	p.Gly317Asp	missense_variant	5/8
DOK7	ENST00000515886.5 linkuse as main transcript	c.452G>A	p.Gly151Asp	missense_variant	4/4	2
DOK7	ENST00000507039.5 linkuse as main transcript	c.*603G>A		3_prime_UTR_variant	7/7	2			Q18PE1-4

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

GnomAD3 exomes

AF:

0.207

AC:

42761

AN:

206948

Hom.:

4684

AF XY:

0.213

AC XY:

24332

AN XY:

114376

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 SAS exome

AF:

0.316

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

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.0912

Gnomad4 SAS exome

AF:

0.319

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.197

GnomAD4 genome

AF:

0.186

AC:

28335

AN:

152250

Hom.:

2813

Cov.:

AF XY:

0.189

AC XY:

14049

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.313

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.186

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 28, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 18, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Fetal akinesia deformation sequence 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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;.;.

MutationTaster

Benign

1.0

P;P;P

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

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