10-22568017-C-T

Variant names:

• chr10-22568017-C-T
• rs2296624
• NM_005028.5:c.640-128G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 = 0.379 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.640-128G>A		intron	N/A	NP_005019.2
	PIP4K2A	NM_001330062.2		c.463-128G>A		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.640-128G>A		intron	N/A	ENSP00000365757.4
	PIP4K2A	ENST00000545335.5	TSL:2	c.463-128G>A		intron	N/A	ENSP00000442098.1
	PIP4K2A	ENST00000323883.11	TSL:2	c.220-128G>A		intron	N/A	ENSP00000326294.7

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

African (AFR) AF: 0.254 AC: 4625 AN: 18230

American (AMR) AF: 0.167 AC: 6657 AN: 39792

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 7605 AN: 19964

East Asian (EAS) AF: 0.387 AC: 13923 AN: 36022

South Asian (SAS) AF: 0.198 AC: 13378 AN: 67480

European-Finnish (FIN) AF: 0.302 AC: 12741 AN: 42172

Middle Eastern (MID) AF: 0.246 AC: 731 AN: 2974

European-Non Finnish (NFE) AF: 0.327 AC: 130058 AN: 398080

Other (OTH) AF: 0.314 AC: 10659 AN: 33984

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

African (AFR) AF: 0.252 AC: 10452 AN: 41540

American (AMR) AF: 0.202 AC: 3095 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3472

East Asian (EAS) AF: 0.393 AC: 2031 AN: 5164

South Asian (SAS) AF: 0.194 AC: 937 AN: 4824

European-Finnish (FIN) AF: 0.296 AC: 3136 AN: 10602

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21941 AN: 67986

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.187 Hom.: 406

Bravo AF: 0.286

Asia WGS AF: 0.276 AC: 961 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	0.23
DANN	Benign	0.65
PhyloP100		-0.60
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: rs2296624; hg19: chr10-22856946; COSMIC: COSV60542203;