Variant 8-21909772-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_003974.4(DOK2):c.778A>G(p.Ile260Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

DOK2
NM_003974.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.856

Variant links:

Genes affected

DOK2 (HGNC:2991): (docking protein 2) The protein encoded by this gene is constitutively tyrosine phosphorylated in hematopoietic progenitors isolated from chronic myelogenous leukemia (CML) patients in the chronic phase. It may be a critical substrate for p210(bcr/abl), a chimeric protein whose presence is associated with CML. This encoded protein binds p120 (RasGAP) from CML cells. [provided by RefSeq, Jul 2008]

DOK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039218515).

BP6

Variant 8-21909772-T-C is Benign according to our data. Variant chr8-21909772-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3273450.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DOK2	NM_003974.4 linkuse as main transcript	c.778A>G	p.Ile260Val	missense_variant	5/5	ENST00000276420.9
DOK2	NM_001401272.1 linkuse as main transcript	c.496A>G	p.Ile166Val	missense_variant	4/4
DOK2	NM_001317800.2 linkuse as main transcript	c.316A>G	p.Ile106Val	missense_variant	3/3
DOK2	NM_201349.3 linkuse as main transcript	c.316A>G	p.Ile106Val	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DOK2	ENST00000276420.9 linkuse as main transcript	c.778A>G	p.Ile260Val	missense_variant	5/5	1	NM_003974.4	P1
DOK2	ENST00000518197.1 linkuse as main transcript	c.316A>G	p.Ile106Val	missense_variant	3/3	1
DOK2	ENST00000524001.1 linkuse as main transcript	n.684A>G		non_coding_transcript_exon_variant	3/3	2
DOK2	ENST00000517422.5 linkuse as main transcript	c.*318A>G		3_prime_UTR_variant, NMD_transcript_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251100

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461680

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.47

DANN

Benign

0.36

DEOGEN2

Benign

0.075

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

-0.64

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

0.010

N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T

Sift4G

Benign

0.90

T;T

Polyphen

0.0

B;.

Vest4

0.039

MutPred

0.10

Loss of glycosylation at P265 (P = 0.2471);.;

MVP

0.71

MPC

0.030

ClinPred

0.014

GERP RS

-0.85

Varity_R

0.015

gMVP

0.19

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