rs7736379

Positions:

• chr5-170083388-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.266 in 152,364 control chromosomes in the GnomAD database, including 7,658 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 0.27 (7653 hom., cov: 32)
  • Exomes 𝑓: 0.13 (5 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

Genes affected

(HGNC:):

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.170083388G>A		intergenic_region
DOCK2	NM_004946.3	c.*530G>A		downstream_gene_variant		ENST00000520908.7	NP_004937.1
DOCK2	NR_156756.1	n.*6G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7	c.*530G>A		downstream_gene_variant		2	NM_004946.3	ENSP00000429283.3

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40375 AN: 151882 Hom.: 7624 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.129 AC: 47 AN: 364 Hom.: 5 Cov.: 0 AF XY: 0.137 AC XY: 31 AN XY: 226

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.0993

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.266 AC: 40457 AN: 152000 Hom.: 7653 Cov.: 32 AF XY: 0.268 AC XY: 19906 AN XY: 74304

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.251

Alfa AF: 0.167 Hom.: 1524

Bravo AF: 0.278

Asia WGS AF: 0.334 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7736379; hg19: chr5-169510392;