5-169714135-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 (★). Synonymous variant affecting the same amino acid position (i.e. V589V) has been classified 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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

DOCK2 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

DOCK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK2	NM_004946.3 link	c.1767T>G	p.Val589Val	synonymous_variant	Exon 18 of 52	ENST00000520908.7	NP_004937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7 link	c.1767T>G	p.Val589Val	synonymous_variant	Exon 18 of 52	2	NM_004946.3	ENSP00000429283.3

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

GnomAD2 exomes

AF:

0.00234

AC:

581

AN:

248572

AF XY:

0.00158

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 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

African (AFR)

AF:

0.0321

AC:

1073

AN:

33470

American (AMR)

AF:

0.00152

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000101

AC:

112

AN:

1111832

Other (OTH)

AF:

0.00230

AC:

139

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

168

253

337

421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00981

AC:

1493

AN:

152252

Hom.:

Cov.:

AF XY:

0.00917

AC XY:

683

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0343

AC:

1426

AN:

41542

American (AMR)

AF:

0.00268

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68010

Other (OTH)

AF:

0.00758

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

143

214

286

357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00125

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

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DOCK2-related disorder

Benign:1

Oct 02, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.65

PhyloP100

-0.55

Mutation Taster

=298/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over