Variant chr4-3463346-G-T 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.-30G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,447,188 control chromosomes in the GnomAD database, including 8,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 678 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8138 hom. )

Consequence

DOK7
NM_173660.5 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.61

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:

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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=-0.77).

BP6

Variant 4-3463346-G-T is Benign according to our data. Variant chr4-3463346-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 262861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3463346-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 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.-30G>T		5_prime_UTR_variant	1/7	ENST00000340083.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK7	ENST00000340083.6 linkuse as main transcript	c.-30G>T		5_prime_UTR_variant	1/7	1	NM_173660.5	P1	Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.0759

AC:

11521

AN:

151812

Hom.:

677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0176

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.0858

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.0280

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.0810

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.0993

Gnomad OTH

AF:

0.0681

GnomAD3 exomes

AF:

0.113

AC:

9379

AN:

83258

Hom.:

698

AF XY:

0.118

AC XY:

5632

AN XY:

47570

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.0322

Gnomad SAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.0818

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.105

AC:

135896

AN:

1295270

Hom.:

8138

Cov.:

AF XY:

0.108

AC XY:

68873

AN XY:

637794

show subpopulations

Gnomad4 AFR exome

AF:

0.0151

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.0213

Gnomad4 SAS exome

AF:

0.231

Gnomad4 FIN exome

AF:

0.0742

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0759

AC:

11527

AN:

151918

Hom.:

678

Cov.:

AF XY:

0.0784

AC XY:

5820

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0175

Gnomad4 AMR

AF:

0.0863

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.0283

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.0810

Gnomad4 NFE

AF:

0.0994

Gnomad4 OTH

AF:

0.0670

Alfa

AF:

0.0438

Hom.:

Bravo

AF:

0.0684

Asia WGS

AF:

0.109

AC:

369

AN:

3368

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 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. -
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

-0.77

CADD

Benign

DANN

Benign

0.83

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