rs1182091

Positions:

• chr5-169952212-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004946.3(DOCK2):​c.2800-30856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,940 control chromosomes in the GnomAD database, including 11,866 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 0.36 (11866 hom., cov: 32)
• Consequence: DOCK2 NM_004946.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSYN2B	NM_001129891.3	c.-919+28065C>T		intron_variant		ENST00000377365.4
DOCK2	NM_004946.3	c.2800-30856G>A		intron_variant		ENST00000520908.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSYN2B	ENST00000377365.4	c.-919+28065C>T		intron_variant		2	NM_001129891.3	P1
DOCK2	ENST00000520908.7	c.2800-30856G>A		intron_variant		2	NM_004946.3	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55175 AN: 151822 Hom.: 11840 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.364 AC: 55246 AN: 151940 Hom.: 11866 Cov.: 32 AF XY: 0.357 AC XY: 26502 AN XY: 74218

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.361

Alfa AF: 0.296 Hom.: 7503

Bravo AF: 0.374

Asia WGS AF: 0.245 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.55

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: rs1182091; hg19: chr5-169379216;