chr5-169930499-T-G

Position:

• chr5-169930499-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004946.3(DOCK2):​c.2800-52569T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,066 control chromosomes in the GnomAD database, including 1,050 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 0.11 (1050 hom., cov: 32)
• Consequence: DOCK2 NM_004946.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.661

Genes affected

INSYN2B (HGNC:37271): (inhibitory synaptic factor family member 2B)

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSYN2B	NM_001129891.3	c.-918-45683A>C		intron_variant		ENST00000377365.4	NP_001123363.1
DOCK2	NM_004946.3	c.2800-52569T>G		intron_variant		ENST00000520908.7	NP_004937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSYN2B	ENST00000377365.4	c.-918-45683A>C		intron_variant		2	NM_001129891.3	ENSP00000366582	P1
DOCK2	ENST00000520908.7	c.2800-52569T>G		intron_variant		2	NM_004946.3	ENSP00000429283	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16450 AN: 151948 Hom.: 1046 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.0144

Gnomad SAS AF: 0.0800

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.108 AC: 16472 AN: 152066 Hom.: 1050 Cov.: 32 AF XY: 0.105 AC XY: 7841 AN XY: 74344

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0716

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.0145

Gnomad4 SAS AF: 0.0799

Gnomad4 FIN AF: 0.0517

Gnomad4 NFE AF: 0.0870

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0931 Hom.: 337

Bravo AF: 0.113

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.71

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: rs259892; hg19: chr5-169357503;