5-170083019-A-G

Variant names:

• chr5-170083019-A-G
• rs9307
• NM_004946.3:c.*161A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004946.3(DOCK2):​c.*161A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 824,482 control chromosomes in the GnomAD database, including 189,889 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (40686 hom., cov: 29)
  • Exomes 𝑓: 0.66 (149203 hom.)
• Consequence: DOCK2 NM_004946.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• DOCK2 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK2	NM_004946.3	c.*161A>G		3_prime_UTR_variant	Exon 52 of 52	ENST00000520908.7	NP_004937.1
DOCK2	NR_156756.1	n.5757A>G		non_coding_transcript_exon_variant	Exon 53 of 53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7	c.*161A>G		3_prime_UTR_variant	Exon 52 of 52	2	NM_004946.3	ENSP00000429283.3

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109765 AN: 151732 Hom.: 40613 Cov.: 29

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.664 AC: 446393 AN: 672632 Hom.: 149203 Cov.: 9 AF XY: 0.662 AC XY: 228680 AN XY: 345470

African (AFR) AF: 0.898 AC: 15618 AN: 17390

American (AMR) AF: 0.691 AC: 18478 AN: 26744

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 10610 AN: 16576

East Asian (EAS) AF: 0.700 AC: 22113 AN: 31600

South Asian (SAS) AF: 0.656 AC: 35249 AN: 53728

European-Finnish (FIN) AF: 0.747 AC: 23225 AN: 31080

Middle Eastern (MID) AF: 0.682 AC: 1737 AN: 2546

European-Non Finnish (NFE) AF: 0.646 AC: 296622 AN: 459450

Other (OTH) AF: 0.678 AC: 22741 AN: 33518

GnomAD4 genome AF: 0.724 AC: 109901 AN: 151850 Hom.: 40686 Cov.: 29 AF XY: 0.725 AC XY: 53782 AN XY: 74224

African (AFR) AF: 0.891 AC: 36917 AN: 41424

American (AMR) AF: 0.664 AC: 10143 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2231 AN: 3466

East Asian (EAS) AF: 0.700 AC: 3554 AN: 5080

South Asian (SAS) AF: 0.669 AC: 3218 AN: 4810

European-Finnish (FIN) AF: 0.755 AC: 7974 AN: 10558

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43498 AN: 67928

Other (OTH) AF: 0.728 AC: 1536 AN: 2110

Alfa AF: 0.675 Hom.: 21340

Bravo AF: 0.725

Asia WGS AF: 0.716 AC: 2492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.75
PhyloP100		-0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9307; hg19: chr5-169510023; COSMIC: COSV56949960; COSMIC: COSV56949960;