rs2043890

Positions:

• chr2-58123436-G-A
• chr2-58123436-G-C
• chr2-58123436-G-T

Variant summary

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

The NM_006296.7(VRK2):​c.676+203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,118 control chromosomes in the GnomAD database, including 42,811 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 0.74 (42811 hom., cov: 32)
• Consequence: VRK2 NM_006296.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

Genes affected

VRK2 (HGNC:12719): (VRK serine/threonine kinase 2) This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. The encoded protein acts as an effector of signaling pathways that regulate apoptosis and tumor cell growth. Variants in this gene have been associated with schizophrenia. Alternative splicing results in multiple transcript variants that differ in their subcellular localization and biological activity. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VRK2	NM_006296.7	c.676+203G>A		intron_variant		ENST00000340157.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VRK2	ENST00000340157.9	c.676+203G>A		intron_variant		1	NM_006296.7	P1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112475 AN: 151998 Hom.: 42753 Cov.: 32

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.740 AC: 112595 AN: 152118 Hom.: 42811 Cov.: 32 AF XY: 0.735 AC XY: 54672 AN XY: 74338

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.708

Alfa AF: 0.730 Hom.: 7888

Bravo AF: 0.748

Asia WGS AF: 0.658 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
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: rs2043890; hg19: chr2-58350571; COSMIC: COSV60881577;