5-169647052-C-T

Variant names:

• chr5-169647052-C-T
• rs169082
• NM_004946.3:c.44-7351C>T

Variant summary

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

The NM_004946.3(DOCK2):​c.44-7351C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,058 control chromosomes in the GnomAD database, including 15,663 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 0.45 (15663 hom., cov: 32)
• Consequence: DOCK2 NM_004946.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK2	NM_004946.3	c.44-7351C>T		intron_variant	Intron 1 of 51	ENST00000520908.7	NP_004937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7	c.44-7351C>T		intron_variant	Intron 1 of 51	2	NM_004946.3	ENSP00000429283.3

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68034 AN: 151940 Hom.: 15664 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.447 AC: 68043 AN: 152058 Hom.: 15663 Cov.: 32 AF XY: 0.447 AC XY: 33232 AN XY: 74308

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.429

Alfa AF: 0.489 Hom.: 42190

Bravo AF: 0.445

Asia WGS AF: 0.429 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.47

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: rs169082; hg19: chr5-169074056;