12-18355318-C-T

Variant names:

• chr12-18355318-C-T
• rs11044045
• NM_001288772.2:c.1626-7446C>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.1626-7446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,150 control chromosomes in the GnomAD database, including 2,047 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 0.15 (2047 hom., cov: 33)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.757
• Publications: 4 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.352 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2G	NM_001288772.2	MANE Select	c.1626-7446C>T		intron	N/A	NP_001275701.1	O75747-1
	PIK3C2G	NM_004570.6		c.1625+8482C>T		intron	N/A	NP_004561.3	O75747-2
	PIK3C2G	NM_001288774.2		c.960-7446C>T		intron	N/A	NP_001275703.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2G	ENST00000538779.6	TSL:5 MANE Select	c.1626-7446C>T		intron	N/A	ENSP00000445381.1	O75747-1
	PIK3C2G	ENST00000546003.5	TSL:1	n.*923-7446C>T		intron	N/A	ENSP00000441618.1	F5GWG6
	PIK3C2G	ENST00000675017.1		c.1626-7446C>T		intron	N/A	ENSP00000501889.1	O75747-1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22166 AN: 152032 Hom.: 2051 Cov.: 33

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.146 AC: 22156 AN: 152150 Hom.: 2047 Cov.: 33 AF XY: 0.149 AC XY: 11054 AN XY: 74366

African (AFR) AF: 0.0472 AC: 1961 AN: 41532

American (AMR) AF: 0.123 AC: 1886 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1799 AN: 5166

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4810

European-Finnish (FIN) AF: 0.136 AC: 1436 AN: 10568

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12231 AN: 68004

Other (OTH) AF: 0.157 AC: 331 AN: 2108

Alfa AF: 0.0914 Hom.: 176

Bravo AF: 0.137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.76
PhyloP100		-0.76
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: rs11044045; hg19: chr12-18508252;