rs4356203

chr11-17138601-A-G

Variant summary

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

The NM_002645.4(PIK3C2A):c.1705-1976T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,930 control chromosomes in the GnomAD database, including 8,860 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 0.31 (8860 hom., cov: 31)
• Consequence: PIK3C2A NM_002645.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83

Genes affected

PIK3C2A (HGNC:8971): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha) The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmanin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3C2A	NM_002645.4	c.1705-1976T>C		intron_variant		ENST00000691414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C2A	ENST00000691414.1	c.1705-1976T>C		intron_variant			NM_002645.4	P1
PIK3C2A	ENST00000265970.11	c.1705-1976T>C		intron_variant		1		P1
PIK3C2A	ENST00000531428.1	n.295+7067T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47242 AN: 151812 Hom.: 8862 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.311 AC: 47244 AN: 151930 Hom.: 8860 Cov.: 31 AF XY: 0.314 AC XY: 23292 AN XY: 74240

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.302

Alfa AF: 0.387 Hom.: 13740

Bravo AF: 0.290

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.7
Dann	Benign	0.62

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: rs4356203; hg19: chr11-17160148;