Genetic Variant PI4K2A:p.Pro15His (chr10-97640786-C-A) – 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_018425.4(PI4K2A):c.44C>A(p.Pro15His) variant causes a missense change. The variant allele was found at a frequency of 0.000000736 in 1,359,158 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P15L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

PI4K2A
NM_018425.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.58

Publications

0 publications found

Variant links:

Genes affected

PI4K2A (HGNC:30031): (phosphatidylinositol 4-kinase type 2 alpha) Phosphatidylinositolpolyphosphates (PtdInsPs) are centrally involved in many biologic processes, ranging from cell growth and organization of the actin cytoskeleton to endo- and exocytosis. PI4KII phosphorylates PtdIns at the D-4 position, an essential step in the biosynthesis of PtdInsPs (Barylko et al., 2001 [PubMed 11244087]).[supplied by OMIM, Mar 2008]

PI4K2A links:

ENSG00000249967 (HGNC:):

ENSG00000249967 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=0.15623993).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018425.4. 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
	PI4K2A	NM_018425.4	MANE Select	c.44C>A	p.Pro15His	missense	Exon 1 of 9	NP_060895.1	Q9BTU6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PI4K2A	ENST00000370631.4	TSL:1 MANE Select	c.44C>A	p.Pro15His	missense	Exon 1 of 9	ENSP00000359665.3	Q9BTU6
ENSG00000249967	ENST00000370649.3	TSL:2	c.346-10155C>A		intron	N/A	ENSP00000359683.3	E9PAM4
PI4K2A	ENST00000880060.1		c.44C>A	p.Pro15His	missense	Exon 1 of 10	ENSP00000550119.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.36e-7

AC:

AN:

1359158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

675080

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28088

American (AMR)

AF:

0.00

AC:

AN:

30804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23136

East Asian (EAS)

AF:

0.00

AC:

AN:

31622

South Asian (SAS)

AF:

0.00

AC:

AN:

75810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3860

European-Non Finnish (NFE)

AF:

9.42e-7

AC:

AN:

1061724

Other (OTH)

AF:

0.00

AC:

AN:

54890

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.0096

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.62

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PhyloP100

4.6

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.24

REVEL

Benign

0.056

Sift

Benign

0.036

Sift4G

Uncertain

0.020

Polyphen

0.17

Vest4

0.33

MutPred

0.14

Loss of glycosylation at P16 (P = 0.0693)

MVP

0.26

MPC

1.4

ClinPred

0.69

GERP RS

4.3

PromoterAI

0.092

Neutral

(source)

Varity_R

0.17

gMVP

0.45

Mutation Taster

=79/21

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over