Variant 20-54591778-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018431.5(DOK5):c.572C>A(p.Thr191Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,460,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

DOK5
NM_018431.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.02

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:

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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=0.23505306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK5	NM_018431.5 linkuse as main transcript	c.572C>A	p.Thr191Asn	missense_variant	5/8	ENST00000262593.10	NP_060901.2	Q9P104-1
DOK5	NM_177959.3 linkuse as main transcript	c.248C>A	p.Thr83Asn	missense_variant	5/8		NP_808874.1	Q9P104-2
DOK5	XM_024451946.2 linkuse as main transcript	c.536C>A	p.Thr179Asn	missense_variant	5/8		XP_024307714.1
DOK5	XM_011528904.2 linkuse as main transcript	c.248C>A	p.Thr83Asn	missense_variant	5/8		XP_011527206.1	Q9P104-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10 linkuse as main transcript	c.572C>A	p.Thr191Asn	missense_variant	5/8	1	NM_018431.5	ENSP00000262593.5		Q9P104-1
DOK5	ENST00000395939.5 linkuse as main transcript	c.248C>A	p.Thr83Asn	missense_variant	5/8	1		ENSP00000379270.1		Q9P104-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249742

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

134934

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460564

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726480

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.572C>A (p.T191N) alteration is located in exon 5 (coding exon 5) of the DOK5 gene. This alteration results from a C to A substitution at nucleotide position 572, causing the threonine (T) at amino acid position 191 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;.

Eigen

Benign

0.037

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.050

N;N

REVEL

Benign

0.27

Sift

Benign

0.20

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.0070

B;B

Vest4

0.34

MutPred

0.37

Loss of phosphorylation at T191 (P = 0.0269);.;

MVP

0.89

MPC

0.45

ClinPred

0.15

GERP RS

5.7

Varity_R

0.23

gMVP

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over