rs11013052

Positions:

• chr10-22573558-C-A

Variant summary

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

The NM_005028.5(PIP4K2A):​c.493-101G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,003,094 control chromosomes in the GnomAD database, including 44,776 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 0.27 (5709 hom., cov: 32)
  • Exomes 𝑓: 0.29 (39067 hom.)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIP4K2A	NM_005028.5	c.493-101G>T		intron_variant		ENST00000376573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.493-101G>T		intron_variant		1	NM_005028.5	P1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40345 AN: 151952 Hom.: 5704 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.294 AC: 250255 AN: 851022 Hom.: 39067 AF XY: 0.291 AC XY: 124946 AN XY: 429246

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.326

Gnomad4 EAS exome AF: 0.0194

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.266 AC: 40391 AN: 152072 Hom.: 5709 Cov.: 32 AF XY: 0.258 AC XY: 19206 AN XY: 74342

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.244

Alfa AF: 0.294 Hom.: 1638

Bravo AF: 0.257

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.1
DANN	Benign	0.64

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: rs11013052; hg19: chr10-22862487;