12-18594594-C-T

Variant names:

• chr12-18594594-C-T
• rs11044211
• NM_001288772.2:c.4087+25C>T

Variant summary

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

The NM_001288772.2(PIK3C2G):​c.4087+25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,204,678 control chromosomes in the GnomAD database, including 44,054 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 0.32 (9130 hom., cov: 32)
  • Exomes 𝑓: 0.25 (34924 hom.)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2G	NM_001288772.2	c.4087+25C>T		intron_variant	Intron 30 of 32	ENST00000538779.6	NP_001275701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2G	ENST00000538779.6	c.4087+25C>T		intron_variant	Intron 30 of 32	5	NM_001288772.2	ENSP00000445381.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48551 AN: 151690 Hom.: 9110 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.305

GnomAD2 exomes AF: 0.267 AC: 44350 AN: 165842 AF XY: 0.261

Gnomad AFR exome AF: 0.557

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.230

Gnomad FIN exome AF: 0.287

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.254 AC: 267454 AN: 1052870 Hom.: 34924 Cov.: 13 AF XY: 0.254 AC XY: 134866 AN XY: 532002

African (AFR) AF: 0.560 AC: 12334 AN: 22008

American (AMR) AF: 0.226 AC: 4824 AN: 21346

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 4035 AN: 20022

East Asian (EAS) AF: 0.224 AC: 7146 AN: 31874

South Asian (SAS) AF: 0.259 AC: 14819 AN: 57324

European-Finnish (FIN) AF: 0.287 AC: 14463 AN: 50432

Middle Eastern (MID) AF: 0.198 AC: 941 AN: 4752

European-Non Finnish (NFE) AF: 0.246 AC: 197081 AN: 799722

Other (OTH) AF: 0.260 AC: 11811 AN: 45390

GnomAD4 genome AF: 0.320 AC: 48625 AN: 151808 Hom.: 9130 Cov.: 32 AF XY: 0.318 AC XY: 23626 AN XY: 74192

African (AFR) AF: 0.540 AC: 22340 AN: 41408

American (AMR) AF: 0.244 AC: 3718 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3466

East Asian (EAS) AF: 0.204 AC: 1052 AN: 5166

South Asian (SAS) AF: 0.230 AC: 1108 AN: 4822

European-Finnish (FIN) AF: 0.268 AC: 2821 AN: 10516

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16107 AN: 67880

Other (OTH) AF: 0.306 AC: 644 AN: 2106

Alfa AF: 0.266 Hom.: 2817

Bravo AF: 0.329

Asia WGS AF: 0.248 AC: 862 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.23
PhyloP100		0.11
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: rs11044211; hg19: chr12-18747528; COSMIC: COSV56810435;