dbSNP rs10508649: PIP4K2A:p.Val199Val (chr10-22573353-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005028.5(PIP4K2A):c.597A>G(p.Val199Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,613,658 control chromosomes in the GnomAD database, including 1,809 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.066 ( 884 hom., cov: 33)

Exomes 𝑓: 0.015 ( 925 hom. )

Consequence

PIP4K2A
NM_005028.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.282

Publications

14 publications found

Variant links:

Genes affected

PIP4K2A (HGNC:8997): (phosphatidylinositol-5-phosphate 4-kinase type 2 alpha) Phosphatidylinositol-5,4-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. [provided by RefSeq, Jul 2008]

PIP4K2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP7

Synonymous conserved (PhyloP=-0.282 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5 link	c.597A>G	p.Val199Val	synonymous_variant	Exon 5 of 10	ENST00000376573.9	NP_005019.2	P48426-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9 link	c.597A>G	p.Val199Val	synonymous_variant	Exon 5 of 10	1	NM_005028.5	ENSP00000365757.4		P48426-1

Frequencies

GnomAD3 genomes

AF:

0.0661

AC:

10059

AN:

152212

Hom.:

881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0312

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.0601

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00948

Gnomad OTH

AF:

0.0430

GnomAD2 exomes

AF:

0.0266

AC:

6670

AN:

250964

AF XY:

0.0220

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.0192

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.0637

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00853

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0153

AC:

22395

AN:

1461328

Hom.:

925

Cov.:

AF XY:

0.0144

AC XY:

10434

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.213

AC:

7129

AN:

33440

American (AMR)

AF:

0.0204

AC:

914

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00333

AC:

AN:

26132

East Asian (EAS)

AF:

0.0426

AC:

1691

AN:

39684

South Asian (SAS)

AF:

0.00860

AC:

742

AN:

86246

European-Finnish (FIN)

AF:

0.00180

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.0199

AC:

115

AN:

5766

European-Non Finnish (NFE)

AF:

0.00911

AC:

10130

AN:

1111554

Other (OTH)

AF:

0.0247

AC:

1491

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

947

1894

2841

3788

4735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

544

1088

1632

2176

2720

<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

AF:

0.0662

AC:

10087

AN:

152330

Hom.:

884

Cov.:

AF XY:

0.0641

AC XY:

4775

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.204

AC:

8478

AN:

41552

American (AMR)

AF:

0.0310

AC:

475

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.0591

AC:

307

AN:

5194

South Asian (SAS)

AF:

0.0118

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00207

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00948

AC:

645

AN:

68038

Other (OTH)

AF:

0.0421

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

428

856

1285

1713

2141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0433

Hom.:

972

Bravo

AF:

0.0767

Asia WGS

AF:

0.0500

AC:

174

AN:

3478

EpiCase

AF:

0.00960

EpiControl

AF:

0.00723

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.2

(source)

DANN

Benign

0.78

PhyloP100

-0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=94/6

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over