Menu
GeneBe

rs149853735

chr5-170027898-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_004946.3(DOCK2):c.3417G>A(p.Glu1139=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,613,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

DOCK2
NM_004946.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0930
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-170027898-G-A is Benign according to our data. Variant chr5-170027898-G-A is described in ClinVar as [Benign]. Clinvar id is 542630.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.093 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0013 (198/152328) while in subpopulation AFR AF= 0.00443 (184/41574). AF 95% confidence interval is 0.0039. There are 0 homozygotes in gnomad4. There are 91 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DOCK2NM_004946.3 linkuse as main transcriptc.3417G>A p.Glu1139= synonymous_variant 34/52 ENST00000520908.7
DOCK2NR_156756.1 linkuse as main transcriptn.3520G>A non_coding_transcript_exon_variant 35/53

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DOCK2ENST00000520908.7 linkuse as main transcriptc.3417G>A p.Glu1139= synonymous_variant 34/522 NM_004946.3 P1Q92608-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00130
AC:
198
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00444
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000315
AC:
79
AN:
250822
Hom.:
0
AF XY:
0.000243
AC XY:
33
AN XY:
135566
show subpopulations
Gnomad AFR exome
AF:
0.00443
Gnomad AMR exome
AF:
0.0000871
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.000491
GnomAD4 exome
AF:
0.000114
AC:
167
AN:
1460986
Hom.:
0
Cov.:
31
AF XY:
0.0000991
AC XY:
72
AN XY:
726802
show subpopulations
Gnomad4 AFR exome
AF:
0.00422
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.000249
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00130
AC:
198
AN:
152328
Hom.:
0
Cov.:
33
AF XY:
0.00122
AC XY:
91
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.00443
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000703
Hom.:
0
Bravo
AF:
0.00174
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

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 submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
4.3
Dann
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs149853735; hg19: chr5-169454902; API