10-22568017-C-T

Position:

• chr10-22568017-C-T

Variant summary

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

The NM_005028.5(PIP4K2A):​c.640-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 810,902 control chromosomes in the GnomAD database, including 38,510 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 0.29 (6702 hom., cov: 33)
  • Exomes 𝑓: 0.30 (31808 hom.)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.640-128G>A		intron_variant		ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.640-128G>A		intron_variant		1	NM_005028.5	ENSP00000365757.4

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44113 AN: 152086 Hom.: 6703 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.304 AC: 200377 AN: 658698 Hom.: 31808 AF XY: 0.300 AC XY: 106317 AN XY: 354250

Gnomad4 AFR exome AF: 0.254

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.387

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.290 AC: 44137 AN: 152204 Hom.: 6702 Cov.: 33 AF XY: 0.284 AC XY: 21138 AN XY: 74402

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.294

Alfa AF: 0.184 Hom.: 382

Bravo AF: 0.286

Asia WGS AF: 0.276 AC: 961 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	0.23
DANN	Benign	0.65

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: rs2296624; hg19: chr10-22856946; COSMIC: COSV60542203;