10-22577963-T-C

Variant names:

• chr10-22577963-T-C
• rs10764338
• NM_005028.5:c.493-4506A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005028.5(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 NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005028.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	NM_005028.5	MANE Select	c.493-4506A>G		intron	N/A	NP_005019.2
	PIP4K2A	NM_001330062.2		c.316-4506A>G		intron	N/A	NP_001316991.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4K2A	ENST00000376573.9	TSL:1 MANE Select	c.493-4506A>G		intron	N/A	ENSP00000365757.4
	PIP4K2A	ENST00000545335.5	TSL:2	c.316-4506A>G		intron	N/A	ENSP00000442098.1
	PIP4K2A	ENST00000323883.11	TSL:2	c.31-4506A>G		intron	N/A	ENSP00000326294.7

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

African (AFR) AF: 0.737 AC: 30562 AN: 41484

American (AMR) AF: 0.860 AC: 13165 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2847 AN: 3472

East Asian (EAS) AF: 0.908 AC: 4713 AN: 5188

South Asian (SAS) AF: 0.826 AC: 3984 AN: 4824

European-Finnish (FIN) AF: 0.892 AC: 9453 AN: 10594

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57729 AN: 68022

Other (OTH) AF: 0.797 AC: 1683 AN: 2112

Alfa AF: 0.837 Hom.: 68096

Bravo AF: 0.815

Asia WGS AF: 0.851 AC: 2958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.71
DANN	Benign	0.63
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10764338; hg19: chr10-22866892;