10-22574562-C-T

Variant names:

• chr10-22574562-C-T
• rs1062190
• NM_005028.5:c.493-1105G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005028.5. 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
	PIP4K2A	NM_005028.5	MANE Select	c.493-1105G>A		intron	N/A	NP_005019.2
	PIP4K2A	NM_001330062.2		c.316-1105G>A		intron	N/A	NP_001316991.1	P48426-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	ENST00000376573.9	TSL:1 MANE Select	c.493-1105G>A		intron	N/A	ENSP00000365757.4	P48426-1
	PIP4K2A	ENST00000899822.1		c.340-1105G>A		intron	N/A	ENSP00000569881.1
	PIP4K2A	ENST00000545335.5	TSL:2	c.316-1105G>A		intron	N/A	ENSP00000442098.1	P48426-2

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

African (AFR) AF: 0.673 AC: 27801 AN: 41322

American (AMR) AF: 0.850 AC: 12970 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2837 AN: 3468

East Asian (EAS) AF: 0.909 AC: 4692 AN: 5162

South Asian (SAS) AF: 0.825 AC: 3971 AN: 4816

European-Finnish (FIN) AF: 0.892 AC: 9345 AN: 10472

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57358 AN: 67966

Other (OTH) AF: 0.781 AC: 1645 AN: 2106

Alfa AF: 0.827 Hom.: 37102

Bravo AF: 0.791

Asia WGS AF: 0.844 AC: 2915 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.56
PhyloP100		0.031
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1062190; hg19: chr10-22863491;