2-57995793-T-C

Position:

• chr2-57995793-T-C

Variant summary

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

The NM_001288837.2(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 NM_001288837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910

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=-0.91).
• 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/exons	MANE	Protein	UniProt
VRK2	NM_001288837.2	c.-556-29872T>C		intron_variant			NP_001275766.1
VRK2	NM_001288838.2	c.-438-29872T>C		intron_variant			NP_001275767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VRK2	ENST00000435505.6	c.-556-29872T>C		intron_variant		1		ENSP00000408002.2
VRK2	ENST00000478687.5	n.189-22223T>C		intron_variant		1
VRK2	ENST00000648897.1	c.-728-22223T>C		intron_variant				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

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.674

Alfa AF: 0.627 Hom.: 64634

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

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: rs2312147; hg19: chr2-58222928;