Variant 4-3473380-G-C 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.101-26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,607,178 control chromosomes in the GnomAD database, including 26,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5174 hom., cov: 34)

Exomes 𝑓: 0.16 ( 21098 hom. )

Consequence

DOK7
NM_173660.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.10

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=-0.94).

BP6

Variant 4-3473380-G-C is Benign according to our data. Variant chr4-3473380-G-C is described in ClinVar as [Benign]. Clinvar id is 262865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK7	NM_173660.5 link	c.101-26G>C		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 link	c.101-26G>C		intron_variant		1	NM_173660.5	ENSP00000344432.5		Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35230

AN:

152088

Hom.:

5157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.133

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.203

GnomAD3 exomes

AF:

0.197

AC:

46805

AN:

237486

Hom.:

5695

AF XY:

0.186

AC XY:

24326

AN XY:

130668

show subpopulations

Gnomad AFR exome

AF:

0.415

Gnomad AMR exome

AF:

0.320

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.297

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.158

AC:

230210

AN:

1454972

Hom.:

21098

Cov.:

AF XY:

0.157

AC XY:

113621

AN XY:

723782

show subpopulations

Gnomad4 AFR exome

AF:

0.428

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.317

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.140

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.232

AC:

35285

AN:

152206

Hom.:

5174

Cov.:

AF XY:

0.231

AC XY:

17207

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.412

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.133

Gnomad4 NFE

AF:

0.146

Gnomad4 OTH

AF:

0.200

Alfa

AF:

0.114

Hom.:

173

ClinVar

Significance: 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. -
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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.074

DANN

Benign

0.29

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