Variant 4-3492722-ACC-AC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_173660.5(DOK7):c.773-32delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.36 ( 10320 hom., cov: 0)

Exomes 𝑓: 0.37 ( 100900 hom. )

Consequence

DOK7
NM_173660.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.80

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 4-3492722-AC-A is Benign according to our data. Variant chr4-3492722-AC-A is described in ClinVar as [Benign]. Clinvar id is 262889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3492722-AC-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 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.773-32delC		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.773-32delC		intron_variant		1	NM_173660.5	ENSP00000344432.5		Q18PE1-1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54782

AN:

151288

Hom.:

10308

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.550

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.374

GnomAD3 exomes

AF:

0.380

AC:

93011

AN:

244512

Hom.:

18227

AF XY:

0.380

AC XY:

50692

AN XY:

133302

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.393

Gnomad EAS exome

AF:

0.540

Gnomad SAS exome

AF:

0.343

Gnomad FIN exome

AF:

0.493

Gnomad NFE exome

AF:

0.371

Gnomad OTH exome

AF:

0.386

GnomAD4 exome

AF:

0.369

AC:

537596

AN:

1458134

Hom.:

100900

Cov.:

AF XY:

0.368

AC XY:

267140

AN XY:

725462

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.324

Gnomad4 ASJ exome

AF:

0.396

Gnomad4 EAS exome

AF:

0.534

Gnomad4 SAS exome

AF:

0.337

Gnomad4 FIN exome

AF:

0.495

Gnomad4 NFE exome

AF:

0.363

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.362

AC:

54829

AN:

151408

Hom.:

10320

Cov.:

AF XY:

0.365

AC XY:

27014

AN XY:

74006

show subpopulations

Gnomad4 AFR

AF:

0.299

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.383

Gnomad4 EAS

AF:

0.550

Gnomad4 SAS

AF:

0.350

Gnomad4 FIN

AF:

0.491

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.378

Alfa

AF:

0.364

Hom.:

1844

Bravo

AF:

0.351

Asia WGS

AF:

0.477

AC:

1659

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

3.0

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