Genetic Variant DOK7:c.773-32delC (chr4-3492722-AC-A) – ACMG Classification: Benign (-16 pts)

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:

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 rank	MANE	Protein	UniProt
DOK7	NM_173660.5 link	c.773-32delC		intron_variant	Intron 6 of 6	ENST00000340083.6	NP_775931.3	Q18PE1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6 link	c.773-36delC		intron_variant	Intron 6 of 6	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

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

4-3492722-ACC-AC

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