rs13155521

Variant names:

• chr5-169747480-A-G
• rs13155521
• NM_004946.3:c.2352A>G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3 BP6_Moderate BA1

The NM_004946.3(DOCK2):​c.2352A>G​(p.Gln784Gln) 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
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.351

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]

ACMG classification

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 rank	MANE	Protein	UniProt
DOCK2	NM_004946.3	c.2352A>G	p.Gln784Gln	synonymous_variant	Exon 23 of 52	ENST00000520908.7	NP_004937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7	c.2352A>G	p.Gln784Gln	synonymous_variant	Exon 23 of 52	2	NM_004946.3	ENSP00000429283.3

Frequencies

GnomAD3 genomes AF: 0.0419 AC: 6372 AN: 152222 Hom.: 191 Cov.: 33

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

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.: 30 AF XY: 0.0623 AC XY: 45250 AN XY: 726778

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.: 33 AF XY: 0.0401 AC XY: 2985 AN XY: 74502

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: 32 AN: 3478

EpiCase AF: 0.0623

EpiControl AF: 0.0621

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

DOCK2 deficiency Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

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	16
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

Other links and lift over

dbSNP: rs13155521; hg19: chr5-169174484;