10-22558510-C-T

Position:

• chr10-22558510-C-T

Variant summary

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

The NM_005028.5(PIP4K2A):​c.679-7738G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,012 control chromosomes in the GnomAD database, including 22,499 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 0.52 (22499 hom., cov: 32)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIP4K2A	NM_005028.5	c.679-7738G>A		intron_variant		ENST00000376573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.679-7738G>A		intron_variant		1	NM_005028.5	P1
PIP4K2A	ENST00000323883.11	c.259-7738G>A		intron_variant		2
PIP4K2A	ENST00000545335.5	c.502-7738G>A		intron_variant		2
PIP4K2A	ENST00000604912.1	c.217-7738G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79460 AN: 151892 Hom.: 22484 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.523 AC: 79485 AN: 152012 Hom.: 22499 Cov.: 32 AF XY: 0.534 AC XY: 39638 AN XY: 74280

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.548

Alfa AF: 0.601 Hom.: 36521

Bravo AF: 0.501

Asia WGS AF: 0.639 AC: 2216 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.52

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: rs7094131; hg19: chr10-22847439;