rs1016771

Variant names:

• chr2-58108546-T-C
• rs1016771
• NM_006296.7:c.544-14555T>C

Variant summary

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

The NM_006296.7(VRK2):​c.544-14555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,868 control chromosomes in the GnomAD database, including 8,777 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 0.31 (8777 hom., cov: 31)
• Consequence: VRK2 NM_006296.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• Publications: 4 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]

ENSG00000303851 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 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.544-14555T>C		intron	N/A	NP_006287.2	Q86Y07-1
	VRK2	NM_001130480.2		c.544-14555T>C		intron	N/A	NP_001123952.1	Q86Y07-1
	VRK2	NM_001130481.2		c.544-14555T>C		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.544-14555T>C		intron	N/A	ENSP00000342381.4	Q86Y07-1
	VRK2	ENST00000435505.6	TSL:1	c.544-14555T>C		intron	N/A	ENSP00000408002.2	Q86Y07-1
	VRK2	ENST00000440705.6	TSL:1	c.475-14555T>C		intron	N/A	ENSP00000398323.2	Q86Y07-3

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47792 AN: 151750 Hom.: 8777 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.315 AC: 47789 AN: 151868 Hom.: 8777 Cov.: 31 AF XY: 0.315 AC XY: 23341 AN XY: 74206

African (AFR) AF: 0.110 AC: 4550 AN: 41474

American (AMR) AF: 0.359 AC: 5466 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1580 AN: 3468

East Asian (EAS) AF: 0.437 AC: 2250 AN: 5150

South Asian (SAS) AF: 0.333 AC: 1599 AN: 4806

European-Finnish (FIN) AF: 0.368 AC: 3876 AN: 10544

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27113 AN: 67918

Other (OTH) AF: 0.350 AC: 734 AN: 2098

Alfa AF: 0.328 Hom.: 1444

Bravo AF: 0.307

Asia WGS AF: 0.324 AC: 1127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.64
PhyloP100		0.24
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: rs1016771; hg19: chr2-58335681;