Variant 5-169714135-T-G 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.1767T>G(p.Val589Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,613,834 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 25 hom., cov: 32)

Exomes 𝑓: 0.00096 ( 16 hom. )

Consequence

DOCK2
NM_004946.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.548

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:

DOCK2 (HGNC:):

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=-0.85).

BP6

Variant 5-169714135-T-G is Benign according to our data. Variant chr5-169714135-T-G is described in ClinVar as [Benign]. Clinvar id is 476003.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.548 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00981 (1493/152252) while in subpopulation AFR AF= 0.0343 (1426/41542). AF 95% confidence interval is 0.0328. There are 25 homozygotes in gnomad4. There are 683 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK2	NM_004946.3 linkuse as main transcript	c.1767T>G	p.Val589Val	synonymous_variant	18/52	ENST00000520908.7	NP_004937.1	Q92608-1Q5XG91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7 linkuse as main transcript	c.1767T>G	p.Val589Val	synonymous_variant	18/52	2	NM_004946.3	ENSP00000429283.3		Q92608-1

Frequencies

GnomAD3 genomes

AF:

0.00980

AC:

1491

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0344

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00234

AC:

581

AN:

248572

Hom.:

AF XY:

0.00158

AC XY:

213

AN XY:

134502

show subpopulations

Gnomad AFR exome

AF:

0.0306

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000180

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.000963

AC:

1408

AN:

1461582

Hom.:

Cov.:

AF XY:

0.000767

AC XY:

558

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.0321

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.00981

AC:

1493

AN:

152252

Hom.:

Cov.:

AF XY:

0.00917

AC XY:

683

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0343

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.000724

Hom.:

Bravo

AF:

0.0110

Asia WGS

AF:

0.00289

AC:

AN:

3476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DOCK2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

DOCK2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.066

DANN

Benign

0.65

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