rs1316638

Positions:

• chr5-170050007-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	Protein	UniProt
DOCK2	NM_004946.3	c.4072-249T>C		intron_variant		ENST00000520908.7	NP_004937.1
DOCK2	NR_156756.1	n.4175-249T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK2	ENST00000520908.7	c.4072-249T>C		intron_variant		2	NM_004946.3	ENSP00000429283	P1

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

Gnomad4 AFR AF: 0.0991

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.147

Alfa AF: 0.133 Hom.: 2414

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

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: rs1316638; hg19: chr5-169477011;