Variant rs114098294 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.5475G>A(p.Ser1825=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,614,170 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 12 hom. )

Consequence

DOCK2
NM_004946.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.17

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-170082840-G-A is Benign according to our data. Variant chr5-170082840-G-A is described in ClinVar as [Benign]. Clinvar id is 542618.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-170082840-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.17 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00624 (951/152300) while in subpopulation AFR AF= 0.0198 (825/41576). AF 95% confidence interval is 0.0187. There are 7 homozygotes in gnomad4. There are 462 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK2	NM_004946.3 linkuse as main transcript	c.5475G>A	p.Ser1825=	synonymous_variant	52/52	ENST00000520908.7	NP_004937.1
DOCK2	NR_156756.1 linkuse as main transcript	n.5578G>A		non_coding_transcript_exon_variant	53/53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7 linkuse as main transcript	c.5475G>A	p.Ser1825=	synonymous_variant	52/52	2	NM_004946.3	ENSP00000429283	P1	Q92608-1

Frequencies

GnomAD3 genomes

AF:

0.00622

AC:

946

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00227

AC:

570

AN:

251246

Hom.:

AF XY:

0.00203

AC XY:

275

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0205

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000863

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00103

AC:

1509

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000998

AC XY:

726

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0186

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000429

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.00624

AC:

951

AN:

152300

Hom.:

Cov.:

AF XY:

0.00620

AC XY:

462

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00296

Hom.:

Bravo

AF:

0.00709

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00107

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.4

DANN

Benign

0.42

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