chr12-18306453-C-T

Variant names:

• chr12-18306453-C-T
• rs12582971
• NM_001288772.2:c.1035-7509C>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.1035-7509C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,936 control chromosomes in the GnomAD database, including 2,135 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 (2135 hom., cov: 31)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 7 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]

RERGL (HGNC:26213): (RERG like) Predicted to enable G protein activity and GTP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2G	NM_001288772.2	c.1035-7509C>T		intron_variant	Intron 5 of 32	ENST00000538779.6	NP_001275701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2G	ENST00000538779.6	c.1035-7509C>T		intron_variant	Intron 5 of 32	5	NM_001288772.2	ENSP00000445381.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22875 AN: 151818 Hom.: 2134 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.151 AC: 22892 AN: 151936 Hom.: 2135 Cov.: 31 AF XY: 0.158 AC XY: 11705 AN XY: 74258

African (AFR) AF: 0.104 AC: 4300 AN: 41506

American (AMR) AF: 0.155 AC: 2357 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3466

East Asian (EAS) AF: 0.460 AC: 2370 AN: 5154

South Asian (SAS) AF: 0.336 AC: 1619 AN: 4822

European-Finnish (FIN) AF: 0.214 AC: 2269 AN: 10580

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9021 AN: 67848

Other (OTH) AF: 0.162 AC: 342 AN: 2108

Alfa AF: 0.143 Hom.: 7670

Bravo AF: 0.148

Asia WGS AF: 0.365 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.46
PhyloP100		-1.3
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: rs12582971; hg19: chr12-18459387;