rs10508649

Positions:

• chr10-22573353-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005028.5(PIP4K2A):​c.597A>G​(p.Val199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,613,658 control chromosomes in the GnomAD database, including 1,809 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 0.066 (884 hom., cov: 33)
  • Exomes 𝑓: 0.015 (925 hom.)
• Consequence: PIP4K2A NM_005028.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.282 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIP4K2A	NM_005028.5	c.597A>G	p.Val199=	synonymous_variant	5/10	ENST00000376573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.597A>G	p.Val199=	synonymous_variant	5/10	1	NM_005028.5	P1

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 10059 AN: 152212 Hom.: 881 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.0601

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00948

Gnomad OTH AF: 0.0430

GnomAD3 exomes AF: 0.0266 AC: 6670 AN: 250964 Hom.: 420 AF XY: 0.0220 AC XY: 2988 AN XY: 135640

Gnomad AFR exome AF: 0.212

Gnomad AMR exome AF: 0.0192

Gnomad ASJ exome AF: 0.00348

Gnomad EAS exome AF: 0.0637

Gnomad SAS exome AF: 0.00873

Gnomad FIN exome AF: 0.00143

Gnomad NFE exome AF: 0.00853

Gnomad OTH exome AF: 0.0150

GnomAD4 exome AF: 0.0153 AC: 22395 AN: 1461328 Hom.: 925 Cov.: 30 AF XY: 0.0144 AC XY: 10434 AN XY: 727000

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.00333

Gnomad4 EAS exome AF: 0.0426

Gnomad4 SAS exome AF: 0.00860

Gnomad4 FIN exome AF: 0.00180

Gnomad4 NFE exome AF: 0.00911

Gnomad4 OTH exome AF: 0.0247

GnomAD4 genome AF: 0.0662 AC: 10087 AN: 152330 Hom.: 884 Cov.: 33 AF XY: 0.0641 AC XY: 4775 AN XY: 74498

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.0591

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.00948

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0266 Hom.: 389

Bravo AF: 0.0767

Asia WGS AF: 0.0500 AC: 174 AN: 3478

EpiCase AF: 0.00960

EpiControl AF: 0.00723

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.2
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs10508649; hg19: chr10-22862282; COSMIC: COSV60542801;