12-18533799-T-C

Variant names:

• chr12-18533799-T-C
• rs7969452
• NM_001288772.2:c.3324-4357T>C

Variant summary

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

The NM_001288772.2(PIK3C2G):​c.3324-4357T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 151,942 control chromosomes in the GnomAD database, including 47,577 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 0.78 (47577 hom., cov: 30)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 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.3324-4357T>C		intron	N/A	NP_001275701.1
	PIK3C2G	NM_004570.6		c.3201-4357T>C		intron	N/A	NP_004561.3
	PIK3C2G	NM_001288774.2		c.2658-4357T>C		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.3324-4357T>C		intron	N/A	ENSP00000445381.1
	PIK3C2G	ENST00000546003.5	TSL:1	n.*2621-4357T>C		intron	N/A	ENSP00000441618.1
	PIK3C2G	ENST00000675017.1		c.3324-4357T>C		intron	N/A	ENSP00000501889.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119033 AN: 151824 Hom.: 47515 Cov.: 30

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.784 AC: 119156 AN: 151942 Hom.: 47577 Cov.: 30 AF XY: 0.789 AC XY: 58599 AN XY: 74250

African (AFR) AF: 0.916 AC: 37984 AN: 41466

American (AMR) AF: 0.795 AC: 12111 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2040 AN: 3466

East Asian (EAS) AF: 0.962 AC: 4947 AN: 5142

South Asian (SAS) AF: 0.824 AC: 3972 AN: 4818

European-Finnish (FIN) AF: 0.780 AC: 8243 AN: 10574

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47586 AN: 67926

Other (OTH) AF: 0.733 AC: 1552 AN: 2116

Alfa AF: 0.731 Hom.: 134081

Bravo AF: 0.790

Asia WGS AF: 0.908 AC: 3159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.50
PhyloP100		-1.6
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: rs7969452; hg19: chr12-18686733;