rs4356203

Variant names:

• chr11-17138601-A-G
• rs4356203
• NM_002645.4:c.1705-1976T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 36 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=-0.86).
• 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 rank	MANE	Protein	UniProt
PIK3C2A	NM_002645.4	c.1705-1976T>C		intron_variant	Intron 8 of 32	ENST00000691414.1	NP_002636.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2A	ENST00000691414.1	c.1705-1976T>C		intron_variant	Intron 8 of 32		NM_002645.4	ENSP00000509400.1
PIK3C2A	ENST00000265970.11	c.1705-1976T>C		intron_variant	Intron 7 of 31	1		ENSP00000265970.6
PIK3C2A	ENST00000531428.1	n.295+7067T>C		intron_variant	Intron 3 of 12	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

African (AFR) AF: 0.112 AC: 4638 AN: 41442

American (AMR) AF: 0.323 AC: 4929 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1256 AN: 3468

East Asian (EAS) AF: 0.134 AC: 693 AN: 5162

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4816

European-Finnish (FIN) AF: 0.476 AC: 5010 AN: 10530

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.419 AC: 28446 AN: 67952

Other (OTH) AF: 0.302 AC: 637 AN: 2110

Alfa AF: 0.376 Hom.: 38143

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
PhyloP100		2.8
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: rs4356203; hg19: chr11-17160148;