rs12827507

Variant names:

• chr12-18594453-A-G
• rs12827507
• NM_001288772.2:c.4012-41A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-18594453-A-G
• chr12-18594453-A-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.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
• Publications: 5 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 (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288772.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2G	NM_001288772.2	MANE Select	c.4012-41A>G		intron	N/A	NP_001275701.1
	PIK3C2G	NM_004570.6		c.3889-41A>G		intron	N/A	NP_004561.3
	PIK3C2G	NM_001288774.2		c.3346-41A>G		intron	N/A	NP_001275703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2G	ENST00000538779.6	TSL:5 MANE Select	c.4012-41A>G		intron	N/A	ENSP00000445381.1
	PIK3C2G	ENST00000546003.5	TSL:1	n.*3309-41A>G		intron	N/A	ENSP00000441618.1
	PIK3C2G	ENST00000675017.1		c.4012-41A>G		intron	N/A	ENSP00000501889.1

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

GnomAD2 exomes AF: 0.197 AC: 32727 AN: 166418 AF XY: 0.200

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 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

African (AFR) AF: 0.0757 AC: 1673 AN: 22110

American (AMR) AF: 0.157 AC: 4030 AN: 25638

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2323 AN: 21976

East Asian (EAS) AF: 0.220 AC: 7362 AN: 33402

South Asian (SAS) AF: 0.219 AC: 14244 AN: 64944

European-Finnish (FIN) AF: 0.240 AC: 12363 AN: 51418

Middle Eastern (MID) AF: 0.0986 AC: 451 AN: 4574

European-Non Finnish (NFE) AF: 0.201 AC: 165125 AN: 820160

Other (OTH) AF: 0.182 AC: 8580 AN: 47270

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

African (AFR) AF: 0.0759 AC: 3152 AN: 41518

American (AMR) AF: 0.152 AC: 2323 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1044 AN: 5158

South Asian (SAS) AF: 0.210 AC: 1014 AN: 4828

European-Finnish (FIN) AF: 0.226 AC: 2394 AN: 10584

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13434 AN: 67918

Other (OTH) AF: 0.166 AC: 350 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.56
PhyloP100		-0.29
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: rs12827507; hg19: chr12-18747387; COSMIC: COSV56811417;