Variant rs17647491 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004946.3(DOCK2):c.4314C>T(p.Tyr1438=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,613,988 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 27 hom., cov: 32)

Exomes 𝑓: 0.017 ( 226 hom. )

Consequence

DOCK2
NM_004946.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.92

Variant links:

Genes affected

DOCK2 (HGNC:2988): (dedicator of cytokinesis 2) The protein encoded by this gene belongs to the CDM protein family. It is specifically expressed in hematopoietic cells and is predominantly expressed in peripheral blood leukocytes. The protein is involved in remodeling of the actin cytoskeleton required for lymphocyte migration in response to chemokine signaling. It activates members of the Rho family of GTPases, for example RAC1 and RAC2, by acting as a guanine nucleotide exchange factor (GEF) to exchange bound GDP for free GTP. Mutations in this gene result in immunodeficiency 40 (IMD40), a combined form of immunodeficiency that affects T cell number and function, also with variable defects in B cell and NK cell function. [provided by RefSeq, May 2018]

DOCK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 5-170056702-C-T is Benign according to our data. Variant chr5-170056702-C-T is described in ClinVar as [Benign]. Clinvar id is 476014.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.92 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.014 (2134/152244) while in subpopulation NFE AF= 0.0211 (1433/68022). AF 95% confidence interval is 0.0202. There are 27 homozygotes in gnomad4. There are 975 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK2	NM_004946.3 linkuse as main transcript	c.4314C>T	p.Tyr1438=	synonymous_variant	43/52	ENST00000520908.7
DOCK2	NR_156756.1 linkuse as main transcript	n.4417C>T		non_coding_transcript_exon_variant	44/53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK2	ENST00000520908.7 linkuse as main transcript	c.4314C>T	p.Tyr1438=	synonymous_variant	43/52	2	NM_004946.3	P1	Q92608-1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2134

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00316

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0166

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0124

AC:

3104

AN:

251276

Hom.:

AF XY:

0.0117

AC XY:

1593

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00289

Gnomad AMR exome

AF:

0.00871

Gnomad ASJ exome

AF:

0.00536

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00203

Gnomad FIN exome

AF:

0.0210

Gnomad NFE exome

AF:

0.0185

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0165

AC:

24121

AN:

1461744

Hom.:

226

Cov.:

AF XY:

0.0160

AC XY:

11633

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.00845

Gnomad4 ASJ exome

AF:

0.00570

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00234

Gnomad4 FIN exome

AF:

0.0205

Gnomad4 NFE exome

AF:

0.0192

Gnomad4 OTH exome

AF:

0.0133

GnomAD4 genome

AF:

0.0140

AC:

2134

AN:

152244

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

975

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00315

Gnomad4 AMR

AF:

0.0192

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0166

Gnomad4 NFE

AF:

0.0211

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0171

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0148

EpiControl

AF:

0.0151

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DOCK2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

3.5

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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