5-170083019-A-G

Position:

• chr5-170083019-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
DOCK2	NM_004946.3	c.*161A>G		3_prime_UTR_variant	52/52	ENST00000520908.7	NP_004937.1
DOCK2	NR_156756.1	n.5757A>G		non_coding_transcript_exon_variant	53/53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7	c.*161A>G		3_prime_UTR_variant	52/52	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

Gnomad4 AFR exome AF: 0.898

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.700

Gnomad4 SAS exome AF: 0.656

Gnomad4 FIN exome AF: 0.747

Gnomad4 NFE exome AF: 0.646

Gnomad4 OTH exome AF: 0.678

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

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.728

Alfa AF: 0.669 Hom.: 13324

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

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