Variant rs77051823 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.331+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,519,254 control chromosomes in the GnomAD database, including 11,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 957 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10652 hom. )

Consequence

DOK7
NM_173660.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.95

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=-0.89).

BP6

Variant 4-3473663-G-A is Benign according to our data. Variant chr4-3473663-G-A is described in ClinVar as [Benign]. Clinvar id is 262873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3473663-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 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.331+27G>A		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.331+27G>A		intron_variant		1	NM_173660.5	ENSP00000344432	P1	Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.0980

AC:

14913

AN:

152176

Hom.:

956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0772

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.122

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.0990

GnomAD3 exomes

AF:

0.135

AC:

18770

AN:

139488

Hom.:

1503

AF XY:

0.132

AC XY:

9805

AN XY:

74194

show subpopulations

Gnomad AFR exome

AF:

0.0220

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.0762

Gnomad EAS exome

AF:

0.236

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.119

AC:

162894

AN:

1366960

Hom.:

10652

Cov.:

AF XY:

0.119

AC XY:

79406

AN XY:

668394

show subpopulations

Gnomad4 AFR exome

AF:

0.0198

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.0722

Gnomad4 EAS exome

AF:

0.272

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.0979

AC:

14907

AN:

152294

Hom.:

957

Cov.:

AF XY:

0.101

AC XY:

7513

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0251

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.0772

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.122

Gnomad4 OTH

AF:

0.0975

Alfa

AF:

0.111

Hom.:

193

Bravo

AF:

0.0972

Asia WGS

AF:

0.131

AC:

453

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	Jun 28, 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

-0.89

CADD

Benign

0.62

DANN

Benign

0.54

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