Genetic Variant PIP4K2A:c.1036+192G>A (chr10-22541612-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005028.5(PIP4K2A):c.1036+192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,860 control chromosomes in the GnomAD database, including 24,958 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 0.56 ( 24958 hom., cov: 30)

Consequence

PIP4K2A
NM_005028.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.803

Publications

11 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5 link	c.1036+192G>A		intron_variant	Intron 8 of 9	ENST00000376573.9	NP_005019.2	P48426-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIP4K2A	ENST00000376573.9 link	c.1036+192G>A	intron_variant	Intron 8 of 9	1	NM_005028.5	ENSP00000365757.4	P48426-1
PIP4K2A	ENST00000545335.5 link	c.859+192G>A	intron_variant	Intron 8 of 9	2		ENSP00000442098.1	P48426-2
PIP4K2A	ENST00000323883.11 link	c.616+192G>A	intron_variant	Intron 6 of 7	2		ENSP00000326294.7	H7BXS3

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

85042

AN:

151742

Hom.:

24942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.709

Gnomad ASJ

AF:

0.535

Gnomad EAS

AF:

0.578

Gnomad SAS

AF:

0.734

Gnomad FIN

AF:

0.636

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.584

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.560

AC:

85090

AN:

151860

Hom.:

24958

Cov.:

AF XY:

0.571

AC XY:

42360

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.369

AC:

15294

AN:

41408

American (AMR)

AF:

0.710

AC:

10825

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.535

AC:

1856

AN:

3470

East Asian (EAS)

AF:

0.579

AC:

2969

AN:

5132

South Asian (SAS)

AF:

0.734

AC:

3535

AN:

4816

European-Finnish (FIN)

AF:

0.636

AC:

6702

AN:

10534

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.620

AC:

42105

AN:

67932

Other (OTH)

AF:

0.585

AC:

1234

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1790

3579

5369

7158

8948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.590

Hom.:

6591

Bravo

AF:

0.550

Asia WGS

AF:

0.645

AC:

2242

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.60

(source)

DANN

Benign

0.75

PhyloP100

-0.80

Mutation Taster

=100/0

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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chr10-22541612-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over