chr10-22550699-T-C

Variant names:

• chr10-22550699-T-C
• rs2230469
• NM_005028.5:c.752A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005028.5(PIP4K2A):​c.752A>G​(p.Asn251Ser) variant causes a missense change. The variant allele was found at a frequency of 0.296 in 1,598,884 control chromosomes in the GnomAD database, including 74,535 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (5183 hom., cov: 32)
  • Exomes 𝑓: 0.30 (69352 hom.)
• Consequence: PIP4K2A NM_005028.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.89
• Publications: 62 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 (MetaRNN=0.0031907558).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	NM_005028.5	MANE Select	c.752A>G	p.Asn251Ser	missense	Exon 7 of 10	NP_005019.2
	PIP4K2A	NM_001330062.2		c.575A>G	p.Asn192Ser	missense	Exon 7 of 10	NP_001316991.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	ENST00000376573.9	TSL:1 MANE Select	c.752A>G	p.Asn251Ser	missense	Exon 7 of 10	ENSP00000365757.4
	PIP4K2A	ENST00000899822.1		c.599A>G	p.Asn200Ser	missense	Exon 6 of 9	ENSP00000569881.1
	PIP4K2A	ENST00000545335.5	TSL:2	c.575A>G	p.Asn192Ser	missense	Exon 7 of 10	ENSP00000442098.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36103 AN: 152040 Hom.: 5190 Cov.: 32

Gnomad AFR AF: 0.0954

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.227

GnomAD2 exomes AF: 0.267 AC: 67168 AN: 251406 AF XY: 0.269

Gnomad AFR exome AF: 0.0918

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.419

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.314

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.302 AC: 437064 AN: 1446726 Hom.: 69352 Cov.: 29 AF XY: 0.299 AC XY: 215672 AN XY: 720464

African (AFR) AF: 0.0847 AC: 2824 AN: 33354

American (AMR) AF: 0.147 AC: 6593 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8428 AN: 26014

East Asian (EAS) AF: 0.401 AC: 15873 AN: 39606

South Asian (SAS) AF: 0.189 AC: 16272 AN: 86036

European-Finnish (FIN) AF: 0.314 AC: 16740 AN: 53390

Middle Eastern (MID) AF: 0.169 AC: 971 AN: 5740

European-Non Finnish (NFE) AF: 0.320 AC: 351855 AN: 1098030

Other (OTH) AF: 0.293 AC: 17508 AN: 59850

GnomAD4 genome AF: 0.237 AC: 36098 AN: 152158 Hom.: 5183 Cov.: 32 AF XY: 0.233 AC XY: 17337 AN XY: 74378

African (AFR) AF: 0.0953 AC: 3956 AN: 41530

American (AMR) AF: 0.171 AC: 2615 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3466

East Asian (EAS) AF: 0.409 AC: 2115 AN: 5172

South Asian (SAS) AF: 0.189 AC: 910 AN: 4820

European-Finnish (FIN) AF: 0.308 AC: 3255 AN: 10574

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21078 AN: 67972

Other (OTH) AF: 0.228 AC: 483 AN: 2116

Alfa AF: 0.287 Hom.: 27865

Bravo AF: 0.227

TwinsUK AF: 0.337 AC: 1249

ALSPAC AF: 0.326 AC: 1257

ESP6500AA AF: 0.104 AC: 456

ESP6500EA AF: 0.319 AC: 2740

ExAC AF: 0.269 AC: 32706

Asia WGS AF: 0.278 AC: 968 AN: 3478

EpiCase AF: 0.294

EpiControl AF: 0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.020	N
PhyloP100		5.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.073
Sift	Benign	0.78	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.15
MPC		0.31
ClinPred		0.044	T
GERP RS		6.1
Varity_R		0.26
gMVP		0.42
Mutation Taster		=83/17	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: rs2230469; hg19: chr10-22839628; COSMIC: COSV60540931;