Variant rs149752614 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018431.5(DOK5):c.707G>A(p.Arg236His) variant causes a missense change. The variant allele was found at a frequency of 0.000175 in 1,539,588 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

DOK5
NM_018431.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.86

Variant links:

Genes affected

DOK5 (HGNC:16173): (docking protein 5) The protein encoded by this gene is a member of the DOK family of membrane proteins, which are adapter proteins involved in signal transduction. The encoded protein interacts with phosphorylated receptor tyrosine kinases to mediate neurite outgrowth and activation of the MAP kinase pathway. Unlike other DOK family proteins, this protein does not interact with RASGAP. This protein is up-regulated in patients with systemic sclerosis and is associated with fibrosis induced by insulin-like growth factor binding protein 5. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jun 2014]

DOK5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0323855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5 link	c.707G>A	p.Arg236His	missense_variant	Exon 6 of 8	ENST00000262593.10	NP_060901.2	Q9P104-1
DOK5	NM_177959.3 link	c.383G>A	p.Arg128His	missense_variant	Exon 6 of 8		NP_808874.1	Q9P104-2
DOK5	XM_024451946.2 link	c.671G>A	p.Arg224His	missense_variant	Exon 6 of 8		XP_024307714.1
DOK5	XM_011528904.2 link	c.383G>A	p.Arg128His	missense_variant	Exon 6 of 8		XP_011527206.1	Q9P104-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10 link	c.707G>A	p.Arg236His	missense_variant	Exon 6 of 8	1	NM_018431.5	ENSP00000262593.5		Q9P104-1
DOK5	ENST00000395939.5 link	c.383G>A	p.Arg128His	missense_variant	Exon 6 of 8	1		ENSP00000379270.1		Q9P104-2

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000208

AC:

AN:

206968

Hom.:

AF XY:

0.000239

AC XY:

AN XY:

112992

show subpopulations

Gnomad AFR exome

AF:

0.0000684

Gnomad AMR exome

AF:

0.0000929

Gnomad ASJ exome

AF:

0.00243

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000208

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000179

AC:

248

AN:

1387354

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

123

AN XY:

686434

show subpopulations

Gnomad4 AFR exome

AF:

0.0000327

Gnomad4 AMR exome

AF:

0.0000930

Gnomad4 ASJ exome

AF:

0.00144

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000182

Gnomad4 OTH exome

AF:

0.000247

GnomAD4 genome

AF:

0.000145

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000264

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000181

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.032

T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.34

Sift

Benign

0.030

D;D

Sift4G

Uncertain

0.042

D;T

Polyphen

0.0020

B;B

Vest4

0.28

MVP

0.93

MPC

0.53

ClinPred

0.36

GERP RS

4.8

Varity_R

0.22

gMVP

0.38

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