rs2699425

Variant summary

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

The NM_173660.5(DOK7):c.332-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 775,664 control chromosomes in the GnomAD database, including 27,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 5709 hom., cov: 17)

Exomes 𝑓: 0.14 ( 22216 hom. )

Consequence

DOK7
NM_173660.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.50

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:

LOC105374355 (HGNC:):

LOC105374355 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 4-3476324-T-C is Benign according to our data. Variant chr4-3476324-T-C is described in ClinVar as [Benign]. Clinvar id is 262875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3476324-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 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.332-18T>C		intron_variant		ENST00000340083.6
LOC105374355	XR_007057994.1 linkuse as main transcript	n.842A>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK7	ENST00000340083.6 linkuse as main transcript	c.332-18T>C		intron_variant		1	NM_173660.5	P1	Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

25727

AN:

91024

Hom.:

5697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.0787

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.0321

AC:

3026

AN:

94144

Hom.:

713

AF XY:

0.0289

AC XY:

1481

AN XY:

51302

show subpopulations

Gnomad AFR exome

AF:

0.0899

Gnomad AMR exome

AF:

0.0429

Gnomad ASJ exome

AF:

0.0231

Gnomad EAS exome

AF:

0.0198

Gnomad SAS exome

AF:

0.0292

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0288

Gnomad OTH exome

AF:

0.0288

GnomAD4 exome

AF:

0.140

AC:

96084

AN:

684598

Hom.:

22216

Cov.:

AF XY:

0.145

AC XY:

49720

AN XY:

342088

show subpopulations

Gnomad4 AFR exome

AF:

0.240

Gnomad4 AMR exome

AF:

0.324

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.237

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.136

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.139

GnomAD4 genome

AF:

0.283

AC:

25759

AN:

91066

Hom.:

5709

Cov.:

AF XY:

0.284

AC XY:

12591

AN XY:

44320

show subpopulations

Gnomad4 AFR

AF:

0.351

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.269

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.199

Gnomad4 NFE

AF:

0.261

Gnomad4 OTH

AF:

0.305

Alfa

AF:

0.413

Hom.:

1242

Bravo

AF:

0.425

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 19, 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	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 1;C1850792:Congenital myasthenic syndrome 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

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

0.51

Dann

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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