5-170054488-T-C

Variant names:

• chr5-170054488-T-C
• rs13361200
• NM_004946.3:c.4214-817T>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.4214-817T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,078 control chromosomes in the GnomAD database, including 17,743 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 0.47 (17743 hom., cov: 33)
• Consequence: DOCK2 NM_004946.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 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.4214-817T>C		intron	N/A	NP_004937.1	Q92608-1
	DOCK2	NR_156756.1		n.4317-817T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK2	ENST00000520908.7	TSL:2 MANE Select	c.4214-817T>C		intron	N/A	ENSP00000429283.3	Q92608-1
	DOCK2	ENST00000524185.5	TSL:1	n.*1169-817T>C		intron	N/A	ENSP00000428850.1	E5RFJ0
	DOCK2	ENST00000961039.1		c.4175-817T>C		intron	N/A	ENSP00000631098.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70854 AN: 151960 Hom.: 17694 Cov.: 33

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.467 AC: 70962 AN: 152078 Hom.: 17743 Cov.: 33 AF XY: 0.466 AC XY: 34642 AN XY: 74348

African (AFR) AF: 0.639 AC: 26492 AN: 41480

American (AMR) AF: 0.507 AC: 7743 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1464 AN: 3470

East Asian (EAS) AF: 0.615 AC: 3177 AN: 5166

South Asian (SAS) AF: 0.549 AC: 2645 AN: 4822

European-Finnish (FIN) AF: 0.326 AC: 3440 AN: 10556

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24549 AN: 67992

Other (OTH) AF: 0.468 AC: 989 AN: 2112

Alfa AF: 0.433 Hom.: 2710

Bravo AF: 0.491

Asia WGS AF: 0.619 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.76
PhyloP100		-0.15
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: rs13361200; hg19: chr5-169481492;