rs12816270

Variant names:

• chr12-18617643-A-G
• rs12816270
• NM_001288772.2:c.4182+8014A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288772.2(PIK3C2G):​c.4182+8014A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,120 control chromosomes in the GnomAD database, including 1,270 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 (1270 hom., cov: 32)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 8 publications found

Genes affected

PIK3C2G (HGNC:8973): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma) 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. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2G	NM_001288772.2	c.4182+8014A>G		intron_variant	Intron 31 of 32	ENST00000538779.6	NP_001275701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2G	ENST00000538779.6	c.4182+8014A>G		intron_variant	Intron 31 of 32	5	NM_001288772.2	ENSP00000445381.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18229 AN: 152002 Hom.: 1273 Cov.: 32

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.120 AC: 18231 AN: 152120 Hom.: 1270 Cov.: 32 AF XY: 0.122 AC XY: 9095 AN XY: 74344

African (AFR) AF: 0.0579 AC: 2404 AN: 41524

American (AMR) AF: 0.130 AC: 1987 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3470

East Asian (EAS) AF: 0.152 AC: 785 AN: 5162

South Asian (SAS) AF: 0.139 AC: 669 AN: 4822

European-Finnish (FIN) AF: 0.175 AC: 1851 AN: 10576

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9939 AN: 67988

Other (OTH) AF: 0.126 AC: 266 AN: 2116

Alfa AF: 0.135 Hom.: 1891

Bravo AF: 0.117

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.70
PhyloP100		0.27
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: rs12816270; hg19: chr12-18770577;