rs11604470

Positions:

• chr11-17191776-T-C

Variant summary

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

The NM_002645.4(PIK3C2A):​c.-66+16072A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,104 control chromosomes in the GnomAD database, including 1,267 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 0.12 (1267 hom., cov: 31)
• Consequence: PIK3C2A NM_002645.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3C2A	NM_002645.4	c.-66+16072A>G		intron_variant		ENST00000691414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C2A	ENST00000691414.1	c.-66+16072A>G		intron_variant			NM_002645.4	P1
PIK3C2A	ENST00000531428.1	n.73+16072A>G		intron_variant, non_coding_transcript_variant		1
PIK3C2A	ENST00000532035.1	c.-66+2613A>G		intron_variant		3
PIK3C2A	ENST00000533645.1	c.-66+16072A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17661 AN: 151986 Hom.: 1265 Cov.: 31

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.116 AC: 17670 AN: 152104 Hom.: 1267 Cov.: 31 AF XY: 0.118 AC XY: 8742 AN XY: 74358

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.0832

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.157

Alfa AF: 0.121 Hom.: 213

Bravo AF: 0.119

Asia WGS AF: 0.0620 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.6
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11604470; hg19: chr11-17213323;