Variant chr4-3485508-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_173660.5(DOK7):c.533-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,549,666 control chromosomes in the GnomAD database, including 689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 77 hom., cov: 34)

Exomes 𝑓: 0.022 ( 612 hom. )

Consequence

DOK7
NM_173660.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.09

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=-0.81).

BP6

Variant 4-3485508-A-G is Benign according to our data. Variant chr4-3485508-A-G is described in ClinVar as [Benign]. Clinvar id is 262879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3485508-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0208 (3159/152234) while in subpopulation NFE AF= 0.0251 (1705/67992). AF 95% confidence interval is 0.0241. There are 77 homozygotes in gnomad4. There are 1736 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 77 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK7	NM_173660.5 linkuse as main transcript	c.533-31A>G		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.533-31A>G		intron_variant		1	NM_173660.5	ENSP00000344432.5		Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3161

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00323

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0996

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0251

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0229

AC:

5060

AN:

220642

Hom.:

151

AF XY:

0.0226

AC XY:

2722

AN XY:

120262

show subpopulations

Gnomad AFR exome

AF:

0.00286

Gnomad AMR exome

AF:

0.00561

Gnomad ASJ exome

AF:

0.00284

Gnomad EAS exome

AF:

0.0000688

Gnomad SAS exome

AF:

0.00379

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.0243

Gnomad OTH exome

AF:

0.0237

GnomAD4 exome

AF:

0.0223

AC:

31111

AN:

1397432

Hom.:

612

Cov.:

AF XY:

0.0219

AC XY:

15115

AN XY:

690442

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00633

Gnomad4 ASJ exome

AF:

0.00273

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00462

Gnomad4 FIN exome

AF:

0.100

Gnomad4 NFE exome

AF:

0.0225

Gnomad4 OTH exome

AF:

0.0176

GnomAD4 genome

AF:

0.0208

AC:

3159

AN:

152234

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1736

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00322

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.0996

Gnomad4 NFE

AF:

0.0251

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0158

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00202

AC:

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2018	- -

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

-0.81

CADD

Benign

2.6

DANN

Benign

0.80

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