rs72841138

Variant names:

• chr5-169689340-G-A
• rs72841138
• NM_004946.3:c.843+7G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-169689340-G-A
• chr5-169689340-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004946.3(DOCK2):​c.843+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 1,613,588 control chromosomes in the GnomAD database, including 1,883 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (186 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1697 hom.)
• Consequence: DOCK2 NM_004946.3 splice_region, intron
• Scores: Splicing: ADA: 0.0003419
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 1.21

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 5-169689340-G-A is Benign according to our data. Variant chr5-169689340-G-A is described in ClinVar as [Benign]. Clinvar id is 476020.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK2	NM_004946.3	c.843+7G>A		splice_region_variant, intron_variant	Intron 9 of 51	ENST00000520908.7	NP_004937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7	c.843+7G>A		splice_region_variant, intron_variant	Intron 9 of 51	2	NM_004946.3	ENSP00000429283.3
DOCK2	ENST00000524185.5	n.843+7G>A		splice_region_variant, intron_variant	Intron 9 of 52	1		ENSP00000428850.1
DOCK2	ENST00000519628.2	c.843+7G>A		splice_region_variant, intron_variant	Intron 9 of 27	3		ENSP00000428841.2
DOCK2	ENST00000522138.2	n.*353+7G>A		splice_region_variant, intron_variant	Intron 9 of 51	3		ENSP00000512484.1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7453 AN: 152088 Hom.: 186 Cov.: 32

Gnomad AFR AF: 0.0685

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0478

GnomAD3 exomes AF: 0.0390 AC: 9782 AN: 250966 Hom.: 239 AF XY: 0.0377 AC XY: 5114 AN XY: 135618

Gnomad AFR exome AF: 0.0707

Gnomad AMR exome AF: 0.0326

Gnomad ASJ exome AF: 0.0556

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0168

Gnomad FIN exome AF: 0.0304

Gnomad NFE exome AF: 0.0482

Gnomad OTH exome AF: 0.0506

GnomAD4 exome AF: 0.0451 AC: 65891 AN: 1461382 Hom.: 1697 Cov.: 30 AF XY: 0.0443 AC XY: 32195 AN XY: 727018

Gnomad4 AFR exome AF: 0.0716

Gnomad4 AMR exome AF: 0.0332

Gnomad4 ASJ exome AF: 0.0577

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0172

Gnomad4 FIN exome AF: 0.0333

Gnomad4 NFE exome AF: 0.0488

Gnomad4 OTH exome AF: 0.0444

GnomAD4 genome AF: 0.0490 AC: 7459 AN: 152206 Hom.: 186 Cov.: 32 AF XY: 0.0468 AC XY: 3487 AN XY: 74442

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0490

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0457 Hom.: 91

Bravo AF: 0.0520

Asia WGS AF: 0.0120 AC: 41 AN: 3476

EpiCase AF: 0.0527

EpiControl AF: 0.0496

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	9.4
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00034
dbscSNV1_RF	Benign	0.016
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

Other links and lift over

dbSNP: rs72841138; hg19: chr5-169116344;