10-22577963-T-C

Position:

• chr10-22577963-T-C

Variant summary

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

The ENST00000376573.9(PIP4K2A):​c.493-4506A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,204 control chromosomes in the GnomAD database, including 51,770 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 0.82 (51770 hom., cov: 32)
• Consequence: PIP4K2A ENST00000376573.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.493-4506A>G		intron_variant		ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.493-4506A>G		intron_variant		1	NM_005028.5	ENSP00000365757	P1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 125083 AN: 152086 Hom.: 51739 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.822 AC: 125170 AN: 152204 Hom.: 51770 Cov.: 32 AF XY: 0.825 AC XY: 61397 AN XY: 74420

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.908

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.797

Alfa AF: 0.841 Hom.: 52576

Bravo AF: 0.815

Asia WGS AF: 0.851 AC: 2958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.71
DANN	Benign	0.63

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: rs10764338; hg19: chr10-22866892;