rs1316638

Variant names:

• chr5-170050007-T-C
• rs1316638
• NM_004946.3:c.4072-249T>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.4072-249T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,144 control chromosomes in the GnomAD database, including 2,142 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 0.15 (2142 hom., cov: 32)
• Consequence: DOCK2 NM_004946.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK2	NM_004946.3	c.4072-249T>C		intron_variant	Intron 40 of 51	ENST00000520908.7	NP_004937.1
DOCK2	NR_156756.1	n.4175-249T>C		intron_variant	Intron 41 of 52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7	c.4072-249T>C		intron_variant	Intron 40 of 51	2	NM_004946.3	ENSP00000429283.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22119 AN: 152026 Hom.: 2129 Cov.: 32

Gnomad AFR AF: 0.0987

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.146 AC: 22165 AN: 152144 Hom.: 2142 Cov.: 32 AF XY: 0.153 AC XY: 11370 AN XY: 74356

African (AFR) AF: 0.0991 AC: 4115 AN: 41520

American (AMR) AF: 0.255 AC: 3895 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3470

East Asian (EAS) AF: 0.483 AC: 2488 AN: 5150

South Asian (SAS) AF: 0.209 AC: 1005 AN: 4820

European-Finnish (FIN) AF: 0.179 AC: 1897 AN: 10602

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7832 AN: 67986

Other (OTH) AF: 0.147 AC: 309 AN: 2108

Alfa AF: 0.134 Hom.: 3037

Bravo AF: 0.156

Asia WGS AF: 0.333 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.66
PhyloP100		-1.3
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: rs1316638; hg19: chr5-169477011;