Variant 4-3485708-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173660.5(DOK7):c.652+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,475,030 control chromosomes in the GnomAD database, including 1,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 969 hom., cov: 34)

Exomes 𝑓: 0.0084 ( 804 hom. )

Consequence

DOK7
NM_173660.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.589

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:

DOK7 (HGNC:):

DOK7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-3485708-G-A is Benign according to our data. Variant chr4-3485708-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK7	NM_173660.5 linkuse as main transcript	c.652+50G>A		intron_variant		ENST00000340083.6	NP_775931.3	Q18PE1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6 linkuse as main transcript	c.652+50G>A		intron_variant		1	NM_173660.5	ENSP00000344432.5		Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.0645

AC:

9812

AN:

152182

Hom.:

965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00340

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.0171

AC:

2261

AN:

132148

Hom.:

180

AF XY:

0.0137

AC XY:

1002

AN XY:

72964

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00469

Gnomad SAS exome

AF:

0.00618

Gnomad FIN exome

AF:

0.0000674

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.00838

AC:

11080

AN:

1322730

Hom.:

804

Cov.:

AF XY:

0.00774

AC XY:

5012

AN XY:

647248

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.0171

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.00273

Gnomad4 SAS exome

AF:

0.00513

Gnomad4 FIN exome

AF:

0.000108

Gnomad4 NFE exome

AF:

0.00251

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.0646

AC:

9835

AN:

152300

Hom.:

969

Cov.:

AF XY:

0.0624

AC XY:

4650

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.0314

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00444

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00340

Gnomad4 OTH

AF:

0.0549

Alfa

AF:

0.0298

Hom.:

Bravo

AF:

0.0724

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	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. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.2

DANN

Benign

0.60

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