rs2043890

Variant names:

• chr2-58123436-G-A
• rs2043890
• NM_006296.7:c.676+203G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006296.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VRK2	NM_006296.7	MANE Select	c.676+203G>A		intron	N/A	NP_006287.2	Q86Y07-1
	VRK2	NM_001130480.2		c.676+203G>A		intron	N/A	NP_001123952.1	Q86Y07-1
	VRK2	NM_001130481.2		c.676+203G>A		intron	N/A	NP_001123953.1	Q86Y07-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VRK2	ENST00000340157.9	TSL:1 MANE Select	c.676+203G>A		intron	N/A	ENSP00000342381.4	Q86Y07-1
	VRK2	ENST00000435505.6	TSL:1	c.676+203G>A		intron	N/A	ENSP00000408002.2	Q86Y07-1
	VRK2	ENST00000440705.6	TSL:1	c.607+203G>A		intron	N/A	ENSP00000398323.2	Q86Y07-3

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

African (AFR) AF: 0.931 AC: 38672 AN: 41546

American (AMR) AF: 0.650 AC: 9937 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2450 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3620 AN: 5164

South Asian (SAS) AF: 0.592 AC: 2848 AN: 4814

European-Finnish (FIN) AF: 0.674 AC: 7121 AN: 10564

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45565 AN: 67968

Other (OTH) AF: 0.708 AC: 1496 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.66
PhyloP100		0.41
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: rs2043890; hg19: chr2-58350571; COSMIC: COSV60881577;