rs375877997

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The ENST00000340083.6(DOK7):c.1029C>T(p.Gly343Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,566,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

DOK7
ENST00000340083.6 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -0.194

Publications

0 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
fetal akinesia deformation sequence 3
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
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

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 4-3493015-C-T is Benign according to our data. Variant chr4-3493015-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 281409.

BP7

Synonymous conserved (PhyloP=-0.194 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000340083.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DOK7	NM_173660.5	MANE Select	c.1029C>T	p.Gly343Gly	synonymous	Exon 7 of 7	NP_775931.3
DOK7	NM_001301071.2		c.1029C>T	p.Gly343Gly	synonymous	Exon 7 of 10	NP_001288000.1
DOK7	NM_001363811.2		c.597C>T	p.Gly199Gly	synonymous	Exon 5 of 8	NP_001350740.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DOK7	ENST00000340083.6	TSL:1 MANE Select	c.1029C>T	p.Gly343Gly	synonymous	Exon 7 of 7	ENSP00000344432.5
DOK7	ENST00000643608.1		c.597C>T	p.Gly199Gly	synonymous	Exon 5 of 8	ENSP00000495701.1
DOK7	ENST00000515886.5	TSL:2	c.99C>T	p.Gly33Gly	synonymous	Exon 4 of 4	ENSP00000492194.1

Frequencies

GnomAD3 genomes

AF:

0.000420

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000413

AC:

AN:

174398

AF XY:

0.000376

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00195

Gnomad EAS exome

AF:

0.000219

Gnomad FIN exome

AF:

0.00400

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.000632

GnomAD4 exome

AF:

0.000207

AC:

293

AN:

1414592

Hom.:

Cov.:

111

AF XY:

0.000203

AC XY:

142

AN XY:

700926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32808

American (AMR)

AF:

0.00

AC:

AN:

38980

Ashkenazi Jewish (ASJ)

AF:

0.00126

AC:

AN:

25440

East Asian (EAS)

AF:

0.000212

AC:

AN:

37764

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81880

European-Finnish (FIN)

AF:

0.00352

AC:

141

AN:

40104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0000906

AC:

AN:

1093050

Other (OTH)

AF:

0.000204

AC:

AN:

58838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000420

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00320

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68018

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000592

Hom.:

Bravo

AF:

0.000125

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

DOK7-related disorder (1)

Fetal akinesia deformation sequence 1;C1850792:Congenital myasthenic syndrome 10 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

-0.19

Mutation Taster

=99/1

polymorphism

(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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over