Variant chr5-169747480-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP6_ModerateBA1

The NM_004946.3(DOCK2):c.2352A>G(p.Gln784=) 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

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 -9 ACMG points.

PP3

Splicing scoreres supports a deletorius 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 id 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/exons	MANE	Protein	UniProt
DOCK2	NM_004946.3 linkuse as main transcript	c.2352A>G	p.Gln784=	synonymous_variant	23/52	ENST00000520908.7	NP_004937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7 linkuse as main transcript	c.2352A>G	p.Gln784=	synonymous_variant	23/52	2	NM_004946.3	ENSP00000429283	P1	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

GnomAD3 exomes

AF:

0.0417

AC:

10442

AN:

250286

Hom.:

308

AF XY:

0.0421

AC XY:

5700

AN XY:

135252

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 SAS exome

AF:

0.0166

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

Gnomad4 AFR exome

AF:

0.00900

Gnomad4 AMR exome

AF:

0.0213

Gnomad4 ASJ exome

AF:

0.0285

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0168

Gnomad4 FIN exome

AF:

0.0443

Gnomad4 NFE exome

AF:

0.0756

Gnomad4 OTH exome

AF:

0.0545

GnomAD4 genome

AF:

0.0418

AC:

6370

AN:

152340

Hom.:

192

Cov.:

AF XY:

0.0401

AC XY:

2985

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.0270

Gnomad4 ASJ

AF:

0.0280

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.0466

Gnomad4 NFE

AF:

0.0685

Gnomad4 OTH

AF:

0.0369

Alfa

AF:

0.0582

Hom.:

517

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

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

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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