10-22643219-T-C

Variant names:

• chr10-22643219-T-C
• rs1778335
• NM_005028.5:c.145-33502A>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.145-33502A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,932 control chromosomes in the GnomAD database, including 5,744 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 (5744 hom., cov: 30)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• Publications: 4 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=-0.99).
• 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 rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.145-33502A>G		intron_variant	Intron 1 of 9	ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.145-33502A>G		intron_variant	Intron 1 of 9	1	NM_005028.5	ENSP00000365757.4
PIP4K2A	ENST00000545335.5	c.-33-33502A>G		intron_variant	Intron 1 of 9	2		ENSP00000442098.1
PIP4K2A	ENST00000605011.1	n.518-1157A>G		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40517 AN: 151814 Hom.: 5726 Cov.: 30

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0318

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.267 AC: 40569 AN: 151932 Hom.: 5744 Cov.: 30 AF XY: 0.263 AC XY: 19542 AN XY: 74266

African (AFR) AF: 0.250 AC: 10371 AN: 41420

American (AMR) AF: 0.184 AC: 2814 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3468

East Asian (EAS) AF: 0.0319 AC: 165 AN: 5176

South Asian (SAS) AF: 0.281 AC: 1349 AN: 4808

European-Finnish (FIN) AF: 0.276 AC: 2919 AN: 10566

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20902 AN: 67912

Other (OTH) AF: 0.245 AC: 517 AN: 2110

Alfa AF: 0.276 Hom.: 1028

Bravo AF: 0.258

Asia WGS AF: 0.164 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.66
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: rs1778335; hg19: chr10-22932148;