Genetic Variant NM_018425.4:c.68G>A (chr10-97640810-G-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.68G>A(p.Gly23Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,318,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

PI4K2A
NM_018425.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.43

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=0.1661253).

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.68G>A	p.Gly23Asp	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.68G>A	p.Gly23Asp	missense	Exon 1 of 9	ENSP00000359665.3	Q9BTU6
ENSG00000249967	ENST00000370649.3	TSL:2	c.346-10131G>A		intron	N/A	ENSP00000359683.3	E9PAM4
PI4K2A	ENST00000880060.1		c.68G>A	p.Gly23Asp	missense	Exon 1 of 10	ENSP00000550119.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.59e-7

AC:

AN:

1318298

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

651718

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27290

American (AMR)

AF:

0.00

AC:

AN:

26500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21504

East Asian (EAS)

AF:

0.00

AC:

AN:

31080

South Asian (SAS)

AF:

0.00

AC:

AN:

68438

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3680

European-Non Finnish (NFE)

AF:

9.62e-7

AC:

AN:

1039516

Other (OTH)

AF:

0.00

AC:

AN:

52934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.057

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

3.4

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.060

REVEL

Benign

0.10

Sift

Benign

0.037

Sift4G

Benign

0.25

Polyphen

0.25

Vest4

0.27

MutPred

0.050

Loss of glycosylation at S22 (P = 0.0992)

MVP

0.39

MPC

1.4

ClinPred

0.66

GERP RS

1.0

PromoterAI

-0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.40

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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