10-22541612-C-T

Variant names:

• chr10-22541612-C-T
• rs746203
• NM_005028.5:c.1036+192G>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.1036+192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,860 control chromosomes in the GnomAD database, including 24,958 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 0.56 (24958 hom., cov: 30)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.803
• Publications: 11 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.1036+192G>A		intron_variant	Intron 8 of 9	ENST00000376573.9	NP_005019.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4K2A	ENST00000376573.9	c.1036+192G>A		intron_variant	Intron 8 of 9	1	NM_005028.5	ENSP00000365757.4
PIP4K2A	ENST00000545335.5	c.859+192G>A		intron_variant	Intron 8 of 9	2		ENSP00000442098.1
PIP4K2A	ENST00000323883.11	c.616+192G>A		intron_variant	Intron 6 of 7	2		ENSP00000326294.7

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85042 AN: 151742 Hom.: 24942 Cov.: 30

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.560 AC: 85090 AN: 151860 Hom.: 24958 Cov.: 30 AF XY: 0.571 AC XY: 42360 AN XY: 74232

African (AFR) AF: 0.369 AC: 15294 AN: 41408

American (AMR) AF: 0.710 AC: 10825 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1856 AN: 3470

East Asian (EAS) AF: 0.579 AC: 2969 AN: 5132

South Asian (SAS) AF: 0.734 AC: 3535 AN: 4816

European-Finnish (FIN) AF: 0.636 AC: 6702 AN: 10534

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42105 AN: 67932

Other (OTH) AF: 0.585 AC: 1234 AN: 2110

Alfa AF: 0.590 Hom.: 6591

Bravo AF: 0.550

Asia WGS AF: 0.645 AC: 2242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.60
DANN	Benign	0.75
PhyloP100		-0.80
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: rs746203; hg19: chr10-22830541; COSMIC: COSV60540945; COSMIC: COSV60540945;