chr10-22590103-G-A

Variant names:

• chr10-22590103-G-A
• rs1409396
• NM_005028.5:c.492+1526C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005028.5(PIP4K2A):​c.492+1526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,994 control chromosomes in the GnomAD database, including 30,786 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 0.63 (30786 hom., cov: 31)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	NM_005028.5	MANE Select	c.492+1526C>T		intron	N/A	NP_005019.2
	PIP4K2A	NM_001330062.2		c.315+1526C>T		intron	N/A	NP_001316991.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	ENST00000376573.9	TSL:1 MANE Select	c.492+1526C>T		intron	N/A	ENSP00000365757.4
	PIP4K2A	ENST00000545335.5	TSL:2	c.315+1526C>T		intron	N/A	ENSP00000442098.1
	PIP4K2A	ENST00000323883.11	TSL:2	c.30+1526C>T		intron	N/A	ENSP00000326294.7

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95643 AN: 151876 Hom.: 30763 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.630 AC: 95715 AN: 151994 Hom.: 30786 Cov.: 31 AF XY: 0.637 AC XY: 47298 AN XY: 74274

African (AFR) AF: 0.678 AC: 28071 AN: 41412

American (AMR) AF: 0.729 AC: 11143 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1804 AN: 3472

East Asian (EAS) AF: 0.943 AC: 4878 AN: 5172

South Asian (SAS) AF: 0.612 AC: 2942 AN: 4804

European-Finnish (FIN) AF: 0.608 AC: 6423 AN: 10556

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38596 AN: 67970

Other (OTH) AF: 0.603 AC: 1276 AN: 2116

Alfa AF: 0.575 Hom.: 12852

Bravo AF: 0.641

Asia WGS AF: 0.776 AC: 2697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.40
PhyloP100		-1.8
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: rs1409396; hg19: chr10-22879032;