12-18594453-A-G

Position:

• chr12-18594453-A-G

Variant summary

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

The NM_001288772.2(PIK3C2G):​c.4012-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,243,532 control chromosomes in the GnomAD database, including 24,540 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 0.16 (2150 hom., cov: 32)
  • Exomes 𝑓: 0.20 (22390 hom.)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3C2G	NM_001288772.2	c.4012-41A>G		intron_variant		ENST00000538779.6	NP_001275701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3C2G	ENST00000538779.6	c.4012-41A>G		intron_variant		5	NM_001288772.2	ENSP00000445381	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24156 AN: 151922 Hom.: 2153 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.197 AC: 32727 AN: 166418 Hom.: 3426 AF XY: 0.200 AC XY: 18435 AN XY: 92292

Gnomad AFR exome AF: 0.0751

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.226

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.198 AC: 216151 AN: 1091492 Hom.: 22390 Cov.: 14 AF XY: 0.198 AC XY: 110055 AN XY: 555380

Gnomad4 AFR exome AF: 0.0757

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.159 AC: 24163 AN: 152040 Hom.: 2150 Cov.: 32 AF XY: 0.161 AC XY: 11950 AN XY: 74330

Gnomad4 AFR AF: 0.0759

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.166

Alfa AF: 0.169 Hom.: 446

Bravo AF: 0.152

Asia WGS AF: 0.203 AC: 705 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.56

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: rs12827507; hg19: chr12-18747387; COSMIC: COSV56811417;