10-22574562-C-T

Position:

• chr10-22574562-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005028.5(PIP4K2A):​c.493-1105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 151,782 control chromosomes in the GnomAD database, including 49,275 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 0.80 (49275 hom., cov: 30)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.493-1105G>A		intron_variant		ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.493-1105G>A		intron_variant		1	NM_005028.5	ENSP00000365757.4

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121574 AN: 151664 Hom.: 49247 Cov.: 30

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.801 AC: 121649 AN: 151782 Hom.: 49275 Cov.: 30 AF XY: 0.806 AC XY: 59764 AN XY: 74184

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.781

Alfa AF: 0.829 Hom.: 27135

Bravo AF: 0.791

Asia WGS AF: 0.844 AC: 2915 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs1062190; hg19: chr10-22863491;