Variant 5-169671132-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1

The NM_004946.3(DOCK2):c.279G>T(p.Thr93Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000712 in 1,614,012 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 1 hom. )

Consequence

DOCK2
NM_004946.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 5-169671132-G-T is Benign according to our data. Variant chr5-169671132-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 476008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00224 (341/152294) while in subpopulation AFR AF= 0.00712 (296/41560). AF 95% confidence interval is 0.00645. There are 1 homozygotes in gnomad4. There are 160 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK2	NM_004946.3 linkuse as main transcript	c.279G>T	p.Thr93Thr	synonymous_variant	5/52	ENST00000520908.7	NP_004937.1	Q92608-1Q5XG91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DOCK2	ENST00000520908.7 linkuse as main transcript	c.279G>T	p.Thr93Thr	synonymous_variant	5/52	2	NM_004946.3	ENSP00000429283.3	Q92608-1
DOCK2	ENST00000524185.5 linkuse as main transcript	n.279G>T		non_coding_transcript_exon_variant	5/53	1		ENSP00000428850.1	E5RFJ0
DOCK2	ENST00000519628.2 linkuse as main transcript	c.279G>T	p.Thr93Thr	synonymous_variant	5/28	3		ENSP00000428841.2	H0YB76
DOCK2	ENST00000522138.2 linkuse as main transcript	n.279G>T		non_coding_transcript_exon_variant	5/52	3		ENSP00000512484.1	A0A8Q3WL64

Frequencies

GnomAD3 genomes

AF:

0.00223

AC:

340

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00712

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000777

AC:

195

AN:

251122

Hom.:

AF XY:

0.000589

AC XY:

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.00689

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000553

AC:

808

AN:

1461718

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

380

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00580

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000410

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00224

AC:

341

AN:

152294

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00712

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000802

Hom.:

Bravo

AF:

0.00279

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.000164

EpiControl

AF:

0.000475

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

DOCK2: BP4, BP7 -

DOCK2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.11

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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