NM_005028.5:c.679-8192T>C

Variant names:

• chr10-22558964-A-G
• rs7081744
• NM_005028.5:c.679-8192T>C

Variant summary

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

The NM_005028.5(PIP4K2A):​c.679-8192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,988 control chromosomes in the GnomAD database, including 23,944 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 0.54 (23944 hom., cov: 32)
• Consequence: PIP4K2A NM_005028.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP4K2A	NM_005028.5	c.679-8192T>C		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.679-8192T>C		intron_variant	Intron 6 of 9	1	NM_005028.5	ENSP00000365757.4
PIP4K2A	ENST00000545335.5	c.502-8192T>C		intron_variant	Intron 6 of 9	2		ENSP00000442098.1
PIP4K2A	ENST00000323883.11	c.259-8192T>C		intron_variant	Intron 4 of 7	2		ENSP00000326294.7
PIP4K2A	ENST00000604912.1	c.217-8192T>C		intron_variant	Intron 3 of 4	2		ENSP00000473858.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81752 AN: 151870 Hom.: 23930 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.538 AC: 81775 AN: 151988 Hom.: 23944 Cov.: 32 AF XY: 0.551 AC XY: 40953 AN XY: 74302

African (AFR) AF: 0.289 AC: 11957 AN: 41436

American (AMR) AF: 0.703 AC: 10724 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3468

East Asian (EAS) AF: 0.614 AC: 3179 AN: 5178

South Asian (SAS) AF: 0.775 AC: 3738 AN: 4824

European-Finnish (FIN) AF: 0.654 AC: 6914 AN: 10566

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41711 AN: 67946

Other (OTH) AF: 0.564 AC: 1191 AN: 2110

Alfa AF: 0.593 Hom.: 32933

Bravo AF: 0.523

Asia WGS AF: 0.675 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		-0.22
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: rs7081744; hg19: chr10-22847893;