Variant rs79063654 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000340083.6(DOK7):c.904G>A(p.Ala302Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A302P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DOK7
ENST00000340083.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.87

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13468757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK7	NM_173660.5 linkuse as main transcript	c.904G>A	p.Ala302Thr	missense_variant	7/7	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.904G>A	p.Ala302Thr	missense_variant	7/7	1	NM_173660.5	ENSP00000344432	P1	Q18PE1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000468

AC:

AN:

213774

Hom.:

AF XY:

0.00

AC XY:

AN XY:

116736

show subpopulations

Gnomad AFR exome

AF:

0.0000771

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1444078

Hom.:

Cov.:

111

AF XY:

0.00000139

AC XY:

AN XY:

717242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.088

T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.068

Sift

Benign

0.15

T;.

Sift4G

Benign

0.28

T;.

Polyphen

0.014

B;.

Vest4

0.069

MutPred

0.28

Loss of glycosylation at P301 (P = 0.0472);.;

MVP

0.48

MPC

0.0068

ClinPred

0.044

GERP RS

1.2

Varity_R

0.043

gMVP

0.089

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over