rs1778329

chr10-22637105-T-C

Variant summary

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

The NM_005028.5(PIP4K2A):c.145-27388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 152,228 control chromosomes in the GnomAD database, including 973 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 0.085 (973 hom., cov: 32)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIP4K2A	NM_005028.5	c.145-27388A>G		intron_variant		ENST00000376573.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.145-27388A>G		intron_variant		1	NM_005028.5	P1
PIP4K2A	ENST00000545335.5	c.-33-27388A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12818 AN: 152110 Hom.: 953 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0846 AC: 12877 AN: 152228 Hom.: 973 Cov.: 32 AF XY: 0.0835 AC XY: 6211 AN XY: 74420

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.0517

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0387

Gnomad4 FIN AF: 0.0312

Gnomad4 NFE AF: 0.0399

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0587 Hom.: 145

Bravo AF: 0.0913

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.49
Dann	Benign	0.37

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: rs1778329; hg19: chr10-22926034;