rs1409396

Positions:

• chr10-22590103-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.492+1526C>T		intron_variant		ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.492+1526C>T		intron_variant		1	NM_005028.5	ENSP00000365757.4

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

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.603

Alfa AF: 0.576 Hom.: 11597

Bravo AF: 0.641

Asia WGS AF: 0.776 AC: 2697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.40

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: rs1409396; hg19: chr10-22879032;