2-57995793-T-C

Variant names:

• chr2-57995793-T-C
• rs2312147
• ENST00000435505.6:c.-556-29872T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000435505.6(VRK2):​c.-556-29872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,088 control chromosomes in the GnomAD database, including 38,005 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 0.70 (38005 hom., cov: 32)
• Consequence: VRK2 ENST00000435505.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• Publications: 43 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]

ENSG00000293612 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VRK2	NM_001288837.2	c.-556-29872T>C		intron_variant	Intron 1 of 15		NP_001275766.1
VRK2	NM_001288838.2	c.-438-29872T>C		intron_variant	Intron 1 of 15		NP_001275767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VRK2	ENST00000435505.6	c.-556-29872T>C		intron_variant	Intron 1 of 15	1		ENSP00000408002.2
VRK2	ENST00000478687.5	n.189-22223T>C		intron_variant	Intron 1 of 5	1
VRK2	ENST00000648897.1	c.-728-22223T>C		intron_variant	Intron 1 of 18			ENSP00000497378.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105793 AN: 151970 Hom.: 37945 Cov.: 32

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.696 AC: 105916 AN: 152088 Hom.: 38005 Cov.: 32 AF XY: 0.693 AC XY: 51500 AN XY: 74342

African (AFR) AF: 0.883 AC: 36640 AN: 41514

American (AMR) AF: 0.628 AC: 9595 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2242 AN: 3464

East Asian (EAS) AF: 0.671 AC: 3470 AN: 5172

South Asian (SAS) AF: 0.584 AC: 2814 AN: 4822

European-Finnish (FIN) AF: 0.639 AC: 6756 AN: 10568

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42120 AN: 67942

Other (OTH) AF: 0.674 AC: 1423 AN: 2112

Alfa AF: 0.639 Hom.: 133622

Bravo AF: 0.704

Asia WGS AF: 0.647 AC: 2253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.74
PhyloP100		-0.91
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: rs2312147; hg19: chr2-58222928;