rs2344209

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173660.5(DOK7):c.101-11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,609,870 control chromosomes in the GnomAD database, including 14,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1378 hom., cov: 34)

Exomes 𝑓: 0.13 ( 13338 hom. )

Consequence

DOK7
NM_173660.5 intron

Scores

Splicing: ADA: 0.0002856

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.14

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 (BayesDel_noAF=-0.79).

BP6

Variant 4-3473395-G-A is Benign according to our data. Variant chr4-3473395-G-A is described in ClinVar as [Benign]. Clinvar id is 262863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3473395-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK7	NM_173660.5 link	c.101-11G>A		intron_variant	Intron 2 of 6	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.101-11G>A		intron_variant	Intron 2 of 6	1	NM_173660.5	ENSP00000344432.5		Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19663

AN:

152148

Hom.:

1378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.0497

Gnomad SAS

AF:

0.0631

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.116

AC:

28051

AN:

242096

Hom.:

1904

AF XY:

0.117

AC XY:

15573

AN XY:

132770

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.0833

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.0498

Gnomad SAS exome

AF:

0.0721

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.131

AC:

191339

AN:

1457604

Hom.:

13338

Cov.:

AF XY:

0.130

AC XY:

94313

AN XY:

725132

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.0890

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.0328

Gnomad4 SAS exome

AF:

0.0710

Gnomad4 FIN exome

AF:

0.105

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.129

AC:

19674

AN:

152266

Hom.:

1378

Cov.:

AF XY:

0.127

AC XY:

9476

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.0496

Gnomad4 SAS

AF:

0.0638

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.137

Hom.:

285

Bravo

AF:

0.133

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -

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

-0.79

CADD

Benign

7.7

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00029

dbscSNV1_RF

Benign

0.022

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