rs11604470

Variant names:

• chr11-17191776-T-C
• rs11604470
• NM_002645.4:c.-66+16072A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

PIK3C2A Gene-Disease associations (from GenCC):

• oculocerebrodental syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002645.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2A	NM_002645.4	MANE Select	c.-66+16072A>G		intron	N/A	NP_002636.2	L7RRS0
	PIK3C2A	NM_001321378.2		c.-66+12531A>G		intron	N/A	NP_001308307.1	O00443-1
	PIK3C2A	NM_001386870.1		c.-66+16072A>G		intron	N/A	NP_001373799.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2A	ENST00000691414.1	MANE Select	c.-66+16072A>G		intron	N/A	ENSP00000509400.1	O00443-1
	PIK3C2A	ENST00000531428.1	TSL:1	n.73+16072A>G		intron	N/A
	PIK3C2A	ENST00000891469.1		c.-66+16072A>G		intron	N/A	ENSP00000561528.1

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

African (AFR) AF: 0.0545 AC: 2265 AN: 41544

American (AMR) AF: 0.218 AC: 3333 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3470

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5176

South Asian (SAS) AF: 0.0832 AC: 401 AN: 4820

European-Finnish (FIN) AF: 0.139 AC: 1465 AN: 10568

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9121 AN: 67954

Other (OTH) AF: 0.157 AC: 331 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.6
DANN	Benign	0.51
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11604470; hg19: chr11-17213323;