rs13155521

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PP3BP6_ModerateBA1

The NM_004946.3(DOCK2):c.2352A>G(p.Gln784Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 1,613,356 control chromosomes in the GnomAD database, including 3,625 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.042 ( 192 hom., cov: 33)

Exomes 𝑓: 0.064 ( 3433 hom. )

Consequence

DOCK2
NM_004946.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.351

Publications

10 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 -9 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 5-169747480-A-G is Benign according to our data. Variant chr5-169747480-A-G is described in ClinVar as Benign. ClinVar VariationId is 476007.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK2	NM_004946.3 link	c.2352A>G	p.Gln784Gln	synonymous_variant	Exon 23 of 52	ENST00000520908.7	NP_004937.1	Q92608-1Q5XG91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7 link	c.2352A>G	p.Gln784Gln	synonymous_variant	Exon 23 of 52	2	NM_004946.3	ENSP00000429283.3		Q92608-1

Frequencies

GnomAD3 genomes

AF:

0.0419

AC:

6372

AN:

152222

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0270

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.0466

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0685

Gnomad OTH

AF:

0.0372

GnomAD2 exomes

AF:

0.0417

AC:

10442

AN:

250286

AF XY:

0.0421

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.0258

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0453

Gnomad NFE exome

AF:

0.0669

Gnomad OTH exome

AF:

0.0405

GnomAD4 exome

AF:

0.0638

AC:

93273

AN:

1461016

Hom.:

3433

Cov.:

AF XY:

0.0623

AC XY:

45250

AN XY:

726778

show subpopulations

African (AFR)

AF:

0.00900

AC:

301

AN:

33450

American (AMR)

AF:

0.0213

AC:

949

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.0285

AC:

745

AN:

26120

East Asian (EAS)

AF:

0.000177

AC:

AN:

39640

South Asian (SAS)

AF:

0.0168

AC:

1449

AN:

86084

European-Finnish (FIN)

AF:

0.0443

AC:

2366

AN:

53382

Middle Eastern (MID)

AF:

0.0212

AC:

122

AN:

5762

European-Non Finnish (NFE)

AF:

0.0756

AC:

84044

AN:

1111552

Other (OTH)

AF:

0.0545

AC:

3290

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

4068

8136

12205

16273

20341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3124

6248

9372

12496

15620

<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:

0.0418

AC:

6370

AN:

152340

Hom.:

192

Cov.:

AF XY:

0.0401

AC XY:

2985

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0122

AC:

507

AN:

41586

American (AMR)

AF:

0.0270

AC:

413

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0280

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.0147

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0466

AC:

495

AN:

10612

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0685

AC:

4657

AN:

68026

Other (OTH)

AF:

0.0369

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

322

644

965

1287

1609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0569

Hom.:

625

Bravo

AF:

0.0405

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0623

EpiControl

AF:

0.0621

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DOCK2 deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.52

PhyloP100

-0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.66

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.66

Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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