NM_004946.3:c.2799+5701G>C

Variant names:

• chr5-169846553-G-C
• rs30080
• NM_004946.3:c.2799+5701G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK2	NM_004946.3	MANE Select	c.2799+5701G>C		intron	N/A	NP_004937.1
	DOCK2	NR_156756.1		n.2851+5701G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK2	ENST00000520908.7	TSL:2 MANE Select	c.2799+5701G>C		intron	N/A	ENSP00000429283.3
	DOCK2	ENST00000524185.5	TSL:1	n.2799+5701G>C		intron	N/A	ENSP00000428850.1
	DOCK2	ENST00000961039.1		c.2760+5701G>C		intron	N/A	ENSP00000631098.1

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

African (AFR) AF: 0.878 AC: 36335 AN: 41390

American (AMR) AF: 0.589 AC: 8979 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2103 AN: 3462

East Asian (EAS) AF: 0.798 AC: 4128 AN: 5174

South Asian (SAS) AF: 0.606 AC: 2919 AN: 4818

European-Finnish (FIN) AF: 0.596 AC: 6244 AN: 10468

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40673 AN: 67910

Other (OTH) AF: 0.679 AC: 1429 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.50
DANN	Benign	0.64
PhyloP100		-1.5
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: rs30080; hg19: chr5-169273557;