10-22536204-T-C

Position:

• chr10-22536204-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.*997A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 398,010 control chromosomes in the GnomAD database, including 92,630 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 0.71 (39226 hom., cov: 32)
  • Exomes 𝑓: 0.66 (53404 hom.)
• Consequence: PIP4K2A NM_005028.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.*997A>G		3_prime_UTR_variant	10/10	ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.*997A>G		3_prime_UTR_variant	10/10	1	NM_005028.5	ENSP00000365757	P1

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108245 AN: 151996 Hom.: 39180 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.656 AC: 161426 AN: 245894 Hom.: 53404 Cov.: 0 AF XY: 0.655 AC XY: 81613 AN XY: 124574

Gnomad4 AFR exome AF: 0.828

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.601

Gnomad4 EAS exome AF: 0.654

Gnomad4 SAS exome AF: 0.771

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.644

Gnomad4 OTH exome AF: 0.675

GnomAD4 genome AF: 0.712 AC: 108357 AN: 152116 Hom.: 39226 Cov.: 32 AF XY: 0.718 AC XY: 53366 AN XY: 74342

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.723

Alfa AF: 0.670 Hom.: 10220

Bravo AF: 0.722

Asia WGS AF: 0.727 AC: 2525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.087
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs8341; hg19: chr10-22825133;