ENST00000412104.6:c.-44A>G

Variant names:

• chr2-58086393-A-G
• rs375372500
• ENST00000412104.6:c.-44A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000412104.6(VRK2):​c.-44A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000206 in 1,453,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: VRK2 ENST00000412104.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4182939).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VRK2	NM_006296.7	c.311A>G	p.Tyr104Cys	missense_variant	Exon 5 of 13	ENST00000340157.9	NP_006287.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VRK2	ENST00000340157.9	c.311A>G	p.Tyr104Cys	missense_variant	Exon 5 of 13	1	NM_006296.7	ENSP00000342381.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453048 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 722662

African (AFR) AF: 0.0000607 AC: 2 AN: 32968

American (AMR) AF: 0.00 AC: 0 AN: 42514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39104

South Asian (SAS) AF: 0.00 AC: 0 AN: 84088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109404

Other (OTH) AF: 0.00 AC: 0 AN: 59998

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	.;T;.;T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.96	D;.;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	M;M;M;M;.
PhyloP100		4.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.2	.;D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.024	.;D;D;D;D
Sift4G	Benign	0.067	.;T;T;T;T
Polyphen		0.99	D;D;D;D;.
Vest4		0.47, 0.47, 0.50, 0.47
MutPred		0.43		Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);.;
MVP		0.74
MPC		0.11
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.40
gMVP		0.70
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs375372500; hg19: chr2-58313528;