rs7905087

Positions:

• chr10-97662891-A-G
• chr10-97662891-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018425.4(PI4K2A):​c.923-16A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,567,704 control chromosomes in the GnomAD database, including 122,466 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 0.41 (12941 hom., cov: 32)
  • Exomes 𝑓: 0.39 (109525 hom.)
• Consequence: PI4K2A NM_018425.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

Genes affected

PI4K2A (HGNC:30031): (phosphatidylinositol 4-kinase type 2 alpha) Phosphatidylinositolpolyphosphates (PtdInsPs) are centrally involved in many biologic processes, ranging from cell growth and organization of the actin cytoskeleton to endo- and exocytosis. PI4KII phosphorylates PtdIns at the D-4 position, an essential step in the biosynthesis of PtdInsPs (Barylko et al., 2001 [PubMed 11244087]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PI4K2A	NM_018425.4	c.923-16A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000370631.4	NP_060895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PI4K2A	ENST00000370631.4	c.923-16A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018425.4	ENSP00000359665	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61693 AN: 151986 Hom.: 12915 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.384

GnomAD3 exomes AF: 0.375 AC: 94276 AN: 251258 Hom.: 18489 AF XY: 0.385 AC XY: 52243 AN XY: 135806

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.317

Gnomad EAS exome AF: 0.353

Gnomad SAS exome AF: 0.501

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.362

GnomAD4 exome AF: 0.389 AC: 551039 AN: 1415600 Hom.: 109525 Cov.: 26 AF XY: 0.394 AC XY: 278272 AN XY: 706976

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.311

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.499

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.406 AC: 61780 AN: 152104 Hom.: 12941 Cov.: 32 AF XY: 0.405 AC XY: 30089 AN XY: 74344

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.345

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.385

Alfa AF: 0.380 Hom.: 12318

Bravo AF: 0.401

Asia WGS AF: 0.442 AC: 1536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.55
DANN	Benign	0.46

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: rs7905087; hg19: chr10-99422648; COSMIC: COSV65701151;