NM_004946.3:c.44-7351C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004946.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK2	NM_004946.3	MANE Select	c.44-7351C>T		intron	N/A	NP_004937.1	Q92608-1
	DOCK2	NR_156756.1		n.96-7351C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK2	ENST00000520908.7	TSL:2 MANE Select	c.44-7351C>T		intron	N/A	ENSP00000429283.3	Q92608-1
	DOCK2	ENST00000524185.5	TSL:1	n.44-7351C>T		intron	N/A	ENSP00000428850.1	E5RFJ0
	DOCK2	ENST00000961039.1		c.44-7351C>T		intron	N/A	ENSP00000631098.1

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

African (AFR) AF: 0.342 AC: 14183 AN: 41468

American (AMR) AF: 0.453 AC: 6923 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3466

East Asian (EAS) AF: 0.528 AC: 2717 AN: 5148

South Asian (SAS) AF: 0.373 AC: 1798 AN: 4814

European-Finnish (FIN) AF: 0.484 AC: 5113 AN: 10574

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34538 AN: 67982

Other (OTH) AF: 0.429 AC: 905 AN: 2110

Alfa AF: 0.487 Hom.: 84513

Bravo AF: 0.445

Asia WGS AF: 0.429 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.47
PhyloP100		0.025
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: rs169082; hg19: chr5-169074056;