Genetic Variant PI4K2B:p.Ser74Cys (chr4-25234384-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018323.4(PI4K2B):c.221C>G(p.Ser74Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000801 in 1,248,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S74F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

PI4K2B
NM_018323.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.52

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1534667).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018323.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PI4K2B	NM_018323.4	MANE Select	c.221C>G	p.Ser74Cys	missense	Exon 1 of 10	NP_060793.2	Q8TCG2
	PI4K2B	NR_144633.2		n.352C>G		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PI4K2B	ENST00000264864.8	TSL:1 MANE Select	c.221C>G	p.Ser74Cys	missense	Exon 1 of 10	ENSP00000264864.6	Q8TCG2
PI4K2B	ENST00000871538.1		c.221C>G	p.Ser74Cys	missense	Exon 1 of 11	ENSP00000541597.1
PI4K2B	ENST00000963199.1		c.221C>G	p.Ser74Cys	missense	Exon 1 of 10	ENSP00000633258.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.01e-7

AC:

AN:

1248166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

608738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25842

American (AMR)

AF:

0.00

AC:

AN:

20904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19772

East Asian (EAS)

AF:

0.00

AC:

AN:

27422

South Asian (SAS)

AF:

0.0000165

AC:

AN:

60472

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3626

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1008602

Other (OTH)

AF:

0.00

AC:

AN:

51334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.1

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.021

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.32

M_CAP

Benign

0.034

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PhyloP100

-2.5

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.1

REVEL

Benign

0.042

Sift

Uncertain

0.018

Sift4G

Uncertain

0.047

Polyphen

0.85

Vest4

0.075

MutPred

0.38

Gain of glycosylation at S78 (P = 0.009)

MVP

0.51

MPC

0.46

ClinPred

0.16

GERP RS

-1.2

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.16

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over