4-3492722-ACC-AC

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 10
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
fetal akinesia deformation sequence 3
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
fetal akinesia deformation sequence 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DOK7 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_173660.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 262889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173660.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOK7	NM_173660.5	MANE Select	c.773-32delC	intron	N/A	NP_775931.3
DOK7	NM_001301071.2		c.773-32delC	intron	N/A	NP_001288000.1	Q18PE1-3
DOK7	NM_001363811.2		c.341-32delC	intron	N/A	NP_001350740.1	A0A2R8Y701

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOK7	ENST00000340083.6	TSL:1 MANE Select	c.773-36delC	intron	N/A	ENSP00000344432.5	Q18PE1-1
DOK7	ENST00000513995.1	TSL:1	n.431-36delC	intron	N/A
DOK7	ENST00000643608.1		c.341-36delC	intron	N/A	ENSP00000495701.1	A0A2R8Y701

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

GnomAD2 exomes

AF:

0.380

AC:

93011

AN:

244512

AF XY:

0.380

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 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

African (AFR)

AF:

0.283

AC:

9458

AN:

33464

American (AMR)

AF:

0.324

AC:

14499

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

10345

AN:

26116

East Asian (EAS)

AF:

0.534

AC:

21179

AN:

39690

South Asian (SAS)

AF:

0.337

AC:

29066

AN:

86222

European-Finnish (FIN)

AF:

0.495

AC:

24814

AN:

50118

Middle Eastern (MID)

AF:

0.370

AC:

2127

AN:

5752

European-Non Finnish (NFE)

AF:

0.363

AC:

403721

AN:

1111744

Other (OTH)

AF:

0.371

AC:

22387

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

22011

44022

66034

88045

110056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12792

25584

38376

51168

63960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.362

AC:

54829

AN:

151408

Hom.:

10320

Cov.:

AF XY:

0.365

AC XY:

27014

AN XY:

74006

show subpopulations

African (AFR)

AF:

0.299

AC:

12236

AN:

40978

American (AMR)

AF:

0.336

AC:

5118

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1330

AN:

3472

East Asian (EAS)

AF:

0.550

AC:

2833

AN:

5152

South Asian (SAS)

AF:

0.350

AC:

1685

AN:

4810

European-Finnish (FIN)

AF:

0.491

AC:

5192

AN:

10568

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.369

AC:

25019

AN:

67866

Other (OTH)

AF:

0.378

AC:

796

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1766

3532

5299

7065

8831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.364

Hom.:

1844

Bravo

AF:

0.351

Asia WGS

AF:

0.477

AC:

1659

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.8

BranchPoint Hunter

3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over