Variant chr2-58123144-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006296.7(VRK2):c.587A>G(p.Asn196Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,598,798 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 2 hom. )

Consequence

VRK2
NM_006296.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

Variant links:

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]

VRK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016452134).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VRK2	NM_006296.7 linkuse as main transcript	c.587A>G	p.Asn196Ser	missense_variant	8/13	ENST00000340157.9	NP_006287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VRK2	ENST00000340157.9 linkuse as main transcript	c.587A>G	p.Asn196Ser	missense_variant	8/13	1	NM_006296.7	ENSP00000342381	P1	Q86Y07-1

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000146

AC:

AN:

233488

Hom.:

AF XY:

0.000134

AC XY:

AN XY:

126494

show subpopulations

Gnomad AFR exome

AF:

0.00189

Gnomad AMR exome

AF:

0.0000333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000752

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000767

AC:

111

AN:

1446580

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

719406

show subpopulations

Gnomad4 AFR exome

AF:

0.00219

Gnomad4 AMR exome

AF:

0.0000493

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000362

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000301

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152218

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00239

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000877

Hom.:

Bravo

AF:

0.000790

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.587A>G (p.N196S) alteration is located in exon 8 (coding exon 7) of the VRK2 gene. This alteration results from a A to G substitution at nucleotide position 587, causing the asparagine (N) at amino acid position 196 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.21

.;T;.;.;T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.65

T;.;T;T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.016

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.89

L;L;L;.;L;.

MutationTaster

Benign

0.98

D;D;D;D;D

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.5

.;N;N;.;N;N

REVEL

Benign

0.071

Sift

Benign

0.050

.;D;T;.;D;D

Sift4G

Uncertain

0.043

.;D;T;T;D;D

Polyphen

0.025

B;B;B;.;B;.

Vest4

0.11, 0.098, 0.074, 0.089, 0.11

MVP

0.25

MPC

0.015

ClinPred

0.028

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.5

Varity_R

0.26

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over