Variant 4-25255065-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018323.4(PI4K2B):c.424A>G(p.Lys142Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000344 in 1,454,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PI4K2B
NM_018323.4 missense, splice_region

Scores

Splicing: ADA: 0.001343

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21

Variant links:

Genes affected

PI4K2B (HGNC:18215): (phosphatidylinositol 4-kinase type 2 beta) This gene encodes a member of the type II PI4 kinase protein family. The encoded protein is primarily cytosolic and contributes to overall PI4-kinase activity along with other protein family members. This protein is involved in early T cell activation. [provided by RefSeq, Dec 2016]

PI4K2B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36807117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PI4K2B	NM_018323.4 linkuse as main transcript	c.424A>G	p.Lys142Glu	missense_variant, splice_region_variant	3/10	ENST00000264864.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4K2B	ENST00000264864.8 linkuse as main transcript	c.424A>G	p.Lys142Glu	missense_variant, splice_region_variant	3/10	1	NM_018323.4
PI4K2B	ENST00000512921.4 linkuse as main transcript	c.136A>G	p.Lys46Glu	missense_variant, splice_region_variant	3/10	2		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249764

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454852

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 16, 2024

The c.424A>G (p.K142E) alteration is located in exon 3 (coding exon 3) of the PI4K2B gene. This alteration results from a A to G substitution at nucleotide position 424, causing the lysine (K) at amino acid position 142 to be replaced by a glutamic acid (E). 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

0.14

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

.;T

Eigen

Benign

0.014

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.1

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.0

D;D

REVEL

Uncertain

0.36

Sift

Benign

0.23

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.080

.;B

Vest4

0.49

MutPred

0.46

.;Loss of methylation at K142 (P = 0.0011);

MVP

0.73

MPC

0.47

ClinPred

0.82

GERP RS

5.0

Varity_R

0.36

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.13

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