chr10-22553439-C-T

Variant names:

• chr10-22553439-C-T
• rs943190
• NM_005028.5:c.679-2667G>A

Variant summary

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

The NM_005028.5(PIP4K2A):​c.679-2667G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,134 control chromosomes in the GnomAD database, including 33,634 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 0.66 (33634 hom., cov: 33)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.679-2667G>A		intron_variant	Intron 6 of 9	ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.679-2667G>A		intron_variant	Intron 6 of 9	1	NM_005028.5	ENSP00000365757.4
PIP4K2A	ENST00000545335.5	c.502-2667G>A		intron_variant	Intron 6 of 9	2		ENSP00000442098.1
PIP4K2A	ENST00000323883.11	c.259-2667G>A		intron_variant	Intron 4 of 7	2		ENSP00000326294.7
PIP4K2A	ENST00000604912.1	c.217-2667G>A		intron_variant	Intron 3 of 4	2		ENSP00000473858.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100659 AN: 152016 Hom.: 33603 Cov.: 33

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.662 AC: 100751 AN: 152134 Hom.: 33634 Cov.: 33 AF XY: 0.668 AC XY: 49716 AN XY: 74382

African (AFR) AF: 0.724 AC: 30050 AN: 41484

American (AMR) AF: 0.749 AC: 11447 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1814 AN: 3468

East Asian (EAS) AF: 0.588 AC: 3041 AN: 5168

South Asian (SAS) AF: 0.770 AC: 3716 AN: 4824

European-Finnish (FIN) AF: 0.637 AC: 6741 AN: 10586

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41964 AN: 67992

Other (OTH) AF: 0.661 AC: 1398 AN: 2116

Alfa AF: 0.643 Hom.: 3883

Bravo AF: 0.667

Asia WGS AF: 0.682 AC: 2367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.024
DANN	Benign	0.51
PhyloP100		-2.8
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: rs943190; hg19: chr10-22842368;