Variant 4-25234426-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018323.4(PI4K2B):c.263T>C(p.Val88Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.4e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PI4K2B
NM_018323.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.752

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04037237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PI4K2B	NM_018323.4 linkuse as main transcript	c.263T>C	p.Val88Ala	missense_variant	1/10	ENST00000264864.8
PI4K2B	XM_005248174.3 linkuse as main transcript	c.263T>C	p.Val88Ala	missense_variant	1/10
PI4K2B	NR_144633.2 linkuse as main transcript	n.394T>C		non_coding_transcript_exon_variant	1/10
PI4K2B	XR_007057941.1 linkuse as main transcript	n.394T>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PI4K2B	ENST00000264864.8 linkuse as main transcript	c.263T>C	p.Val88Ala	missense_variant	1/10	1	NM_018323.4
PI4K2B	ENST00000512921.4 linkuse as main transcript	c.-20-17895T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

8.40e-7

AC:

AN:

1190786

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

576624

show subpopulations

Gnomad4 AFR exome

AF:

0.0000412

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

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

Aug 02, 2023

The c.263T>C (p.V88A) alteration is located in exon 1 (coding exon 1) of the PI4K2B gene. This alteration results from a T to C substitution at nucleotide position 263, causing the valine (V) at amino acid position 88 to be replaced by an alanine (A). 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

0.059

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.48

DANN

Benign

0.59

DEOGEN2

Benign

0.0041

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.18

M_CAP

Benign

0.0065

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.0

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

0.95

Polyphen

0.0020

Vest4

0.043

MutPred

0.62

Loss of glycosylation at T91 (P = 0.023);

MVP

0.061

MPC

0.38

ClinPred

0.036

GERP RS

-5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over