Variant rs2270895 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004946.3(DOCK2):c.3756+94A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,167,328 control chromosomes in the GnomAD database, including 135,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.42 ( 14571 hom., cov: 32)

Exomes 𝑓: 0.48 ( 120738 hom. )

Consequence

DOCK2
NM_004946.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.255

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 -14 ACMG points.

BP4

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

BP6

Variant 5-170041239-A-G is Benign according to our data. Variant chr5-170041239-A-G is described in ClinVar as [Benign]. Clinvar id is 2688034.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 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.3756+94A>G		intron_variant		ENST00000520908.7	NP_004937.1
DOCK2	NR_156756.1 linkuse as main transcript	n.3859+94A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7 linkuse as main transcript	c.3756+94A>G		intron_variant		2	NM_004946.3	ENSP00000429283	P1	Q92608-1

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63735

AN:

151866

Hom.:

14552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.620

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.421

GnomAD4 exome

AF:

0.481

AC:

488104

AN:

1015344

Hom.:

120738

AF XY:

0.485

AC XY:

250934

AN XY:

517830

show subpopulations

Gnomad4 AFR exome

AF:

0.231

Gnomad4 AMR exome

AF:

0.544

Gnomad4 ASJ exome

AF:

0.494

Gnomad4 EAS exome

AF:

0.621

Gnomad4 SAS exome

AF:

0.567

Gnomad4 FIN exome

AF:

0.530

Gnomad4 NFE exome

AF:

0.467

Gnomad4 OTH exome

AF:

0.469

GnomAD4 genome

AF:

0.420

AC:

63781

AN:

151984

Hom.:

14571

Cov.:

AF XY:

0.430

AC XY:

31959

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.474

Gnomad4 ASJ

AF:

0.493

Gnomad4 EAS

AF:

0.620

Gnomad4 SAS

AF:

0.573

Gnomad4 FIN

AF:

0.548

Gnomad4 NFE

AF:

0.468

Gnomad4 OTH

AF:

0.426

Alfa

AF:

0.459

Hom.:

20618

Bravo

AF:

0.409

Asia WGS

AF:

0.620

AC:

2157

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 66% of patients studied by a panel of primary immunodeficiencies. Number of patients: 63. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.2

DANN

Benign

0.82

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