Genetic Variant PI4K2A:p.Ala79Val (chr10-97640978-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018425.4(PI4K2A):c.236C>T(p.Ala79Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 1,527,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

PI4K2A
NM_018425.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.216

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077997655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PI4K2A	NM_018425.4 link	c.236C>T	p.Ala79Val	missense_variant	Exon 1 of 9	ENST00000370631.4	NP_060895.1	Q9BTU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PI4K2A	ENST00000370631.4 link	c.236C>T	p.Ala79Val	missense_variant	Exon 1 of 9	1	NM_018425.4	ENSP00000359665.3		Q9BTU6
ENSG00000249967	ENST00000370649.3 link	c.346-9963C>T		intron_variant	Intron 2 of 9	2		ENSP00000359683.3		E9PAM4

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151688

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1375434

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

678720

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151688

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.236C>T (p.A79V) alteration is located in exon 1 (coding exon 1) of the PI4K2A gene. This alteration results from a C to T substitution at nucleotide position 236, causing the alanine (A) at amino acid position 79 to be replaced by a valine (V). 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

0.093

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.12

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.030

REVEL

Benign

0.041

Sift

Benign

0.20

Sift4G

Benign

0.48

Polyphen

0.0090

Vest4

0.089

MutPred

0.24

Loss of helix (P = 0.0196);

MVP

0.19

MPC

1.1

ClinPred

0.16

GERP RS

1.6

Varity_R

0.092

gMVP

0.33

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

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