rs7088318

Positions:

• chr10-22564019-C-A
• chr10-22564019-C-G

Variant summary

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

The NM_005028.5(PIP4K2A):​c.678+3832G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,986 control chromosomes in the GnomAD database, including 24,733 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 0.56 (24733 hom., cov: 32)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.678+3832G>T		intron_variant		ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.678+3832G>T		intron_variant		1	NM_005028.5	ENSP00000365757	P1
PIP4K2A	ENST00000323883.11	c.258+3832G>T		intron_variant		2		ENSP00000326294
PIP4K2A	ENST00000545335.5	c.501+3832G>T		intron_variant		2		ENSP00000442098
PIP4K2A	ENST00000604912.1	c.216+3832G>T		intron_variant		2		ENSP00000473858

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85019 AN: 151866 Hom.: 24718 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.560 AC: 85052 AN: 151986 Hom.: 24733 Cov.: 32 AF XY: 0.571 AC XY: 42387 AN XY: 74262

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.583

Alfa AF: 0.600 Hom.: 62122

Bravo AF: 0.549

Asia WGS AF: 0.659 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.69

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: rs7088318; hg19: chr10-22852948;