Variant rs2006791 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.533-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,549,968 control chromosomes in the GnomAD database, including 405,822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41746 hom., cov: 33)

Exomes 𝑓: 0.72 ( 364076 hom. )

Consequence

DOK7
NM_173660.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.339

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=-0.87).

BP6

Variant 4-3485510-A-G is Benign according to our data. Variant chr4-3485510-A-G is described in ClinVar as [Benign]. Clinvar id is 262878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 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.533-29A>G		intron_variant		ENST00000340083.6	NP_775931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6 linkuse as main transcript	c.533-29A>G		intron_variant		1	NM_173660.5	ENSP00000344432	P1	Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.738

AC:

112131

AN:

152014

Hom.:

41692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.720

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.737

Gnomad EAS

AF:

0.932

Gnomad SAS

AF:

0.815

Gnomad FIN

AF:

0.791

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.702

Gnomad OTH

AF:

0.744

GnomAD3 exomes

AF:

0.765

AC:

168870

AN:

220616

Hom.:

65378

AF XY:

0.761

AC XY:

91519

AN XY:

120248

show subpopulations

Gnomad AFR exome

AF:

0.728

Gnomad AMR exome

AF:

0.858

Gnomad ASJ exome

AF:

0.734

Gnomad EAS exome

AF:

0.935

Gnomad SAS exome

AF:

0.811

Gnomad FIN exome

AF:

0.788

Gnomad NFE exome

AF:

0.706

Gnomad OTH exome

AF:

0.754

GnomAD4 exome

AF:

0.719

AC:

1005208

AN:

1397836

Hom.:

364076

Cov.:

AF XY:

0.722

AC XY:

498361

AN XY:

690728

show subpopulations

Gnomad4 AFR exome

AF:

0.727

Gnomad4 AMR exome

AF:

0.849

Gnomad4 ASJ exome

AF:

0.730

Gnomad4 EAS exome

AF:

0.942

Gnomad4 SAS exome

AF:

0.813

Gnomad4 FIN exome

AF:

0.784

Gnomad4 NFE exome

AF:

0.696

Gnomad4 OTH exome

AF:

0.729

GnomAD4 genome

AF:

0.738

AC:

112241

AN:

152132

Hom.:

41746

Cov.:

AF XY:

0.746

AC XY:

55505

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.720

Gnomad4 AMR

AF:

0.808

Gnomad4 ASJ

AF:

0.737

Gnomad4 EAS

AF:

0.931

Gnomad4 SAS

AF:

0.816

Gnomad4 FIN

AF:

0.791

Gnomad4 NFE

AF:

0.702

Gnomad4 OTH

AF:

0.746

Alfa

AF:

0.717

Hom.:

7249

Bravo

AF:

0.738

Asia WGS

AF:

0.861

AC:

2996

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 16, 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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital myasthenic syndrome 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Fetal akinesia deformation sequence 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Benign

0.71

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