Variant 4-25259085-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_018323.4(PI4K2B):c.805T>C(p.Trp269Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,441,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PI4K2B
NM_018323.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.89

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:

PI4K2B (HGNC:):

PI4K2B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PI4K2B	NM_018323.4 linkuse as main transcript	c.805T>C	p.Trp269Arg	missense_variant	5/10	ENST00000264864.8	NP_060793.2	Q8TCG2
PI4K2B	XM_005248174.3 linkuse as main transcript	c.790T>C	p.Trp264Arg	missense_variant	5/10		XP_005248231.1
PI4K2B	XM_005248175.5 linkuse as main transcript	c.517T>C	p.Trp173Arg	missense_variant	5/10		XP_005248232.1	G5E9Z4
PI4K2B	NR_144633.2 linkuse as main transcript	n.951T>C		non_coding_transcript_exon_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PI4K2B	ENST00000264864.8 linkuse as main transcript	c.805T>C	p.Trp269Arg	missense_variant	5/10	1	NM_018323.4	ENSP00000264864.6		Q8TCG2
PI4K2B	ENST00000512921.4 linkuse as main transcript	c.517T>C	p.Trp173Arg	missense_variant	5/10	2		ENSP00000423373.1		G5E9Z4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000799

AC:

AN:

250274

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1441356

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718504

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000354

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000741

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

Dec 19, 2023

The c.805T>C (p.W269R) alteration is located in exon 5 (coding exon 5) of the PI4K2B gene. This alteration results from a T to C substitution at nucleotide position 805, causing the tryptophan (W) at amino acid position 269 to be replaced by an arginine (R). 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

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

.;T

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Uncertain

0.66

MutationAssessor

Pathogenic

3.8

.;H

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-13

D;D

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

1.0

.;D

Vest4

0.93

MutPred

0.71

.;Gain of loop (P = 3e-04);

MVP

0.90

MPC

1.3

ClinPred

0.95

GERP RS

5.3

Varity_R

0.90

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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