5-169846553-G-C

Position:

• chr5-169846553-G-C

Variant summary

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

The NM_004946.3(DOCK2):​c.2799+5701G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 151,778 control chromosomes in the GnomAD database, including 36,565 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 0.68 (36565 hom., cov: 30)
• Consequence: DOCK2 NM_004946.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK2	NM_004946.3	c.2799+5701G>C		intron_variant		ENST00000520908.7	NP_004937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7	c.2799+5701G>C		intron_variant		2	NM_004946.3	ENSP00000429283.3

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103460 AN: 151660 Hom.: 36503 Cov.: 30

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.675

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.682 AC: 103582 AN: 151778 Hom.: 36565 Cov.: 30 AF XY: 0.678 AC XY: 50283 AN XY: 74118

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.679

Alfa AF: 0.631 Hom.: 3695

Bravo AF: 0.690

Asia WGS AF: 0.694 AC: 2414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.50
DANN	Benign	0.64

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: rs30080; hg19: chr5-169273557;