2-57926541-G-T

Position:

• chr2-57926541-G-T

Variant summary

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

The ENST00000435505.6(VRK2):​c.-557+18702G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 149,590 control chromosomes in the GnomAD database, including 2,213 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 0.16 (2213 hom., cov: 29)
• Consequence: VRK2 ENST00000435505.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VRK2	NM_001288837.2	c.-557+18702G>T		intron_variant			NP_001275766.1
VRK2	NM_001288838.2	c.-439+18702G>T		intron_variant			NP_001275767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VRK2	ENST00000435505.6	c.-557+18702G>T		intron_variant		1		ENSP00000408002	P1
VRK2	ENST00000478687.5	n.188+18702G>T		intron_variant, non_coding_transcript_variant		1
VRK2	ENST00000417641.6	c.-439+18702G>T		intron_variant		2		ENSP00000402375

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24185 AN: 149490 Hom.: 2205 Cov.: 29

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.162 AC: 24215 AN: 149590 Hom.: 2213 Cov.: 29 AF XY: 0.159 AC XY: 11625 AN XY: 72986

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0905

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.169

Alfa AF: 0.130 Hom.: 1517

Bravo AF: 0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.26
DANN	Benign	0.28

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: rs10189138; hg19: chr2-58153676; COSMIC: COSV70246148;