rs2305220

Positions:

• chr12-18498768-G-A
• chr12-18498768-G-C
• chr12-18498768-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288772.2(PIK3C2G):​c.3016+1020G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,812 control chromosomes in the GnomAD database, including 12,945 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 0.40 (12945 hom., cov: 31)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3C2G	NM_001288772.2	c.3016+1020G>A		intron_variant		ENST00000538779.6	NP_001275701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3C2G	ENST00000538779.6	c.3016+1020G>A		intron_variant		5	NM_001288772.2	ENSP00000445381	P1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61202 AN: 151694 Hom.: 12918 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.343

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.404 AC: 61282 AN: 151812 Hom.: 12945 Cov.: 31 AF XY: 0.401 AC XY: 29731 AN XY: 74154

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.403

Alfa AF: 0.361 Hom.: 15759

Bravo AF: 0.415

Asia WGS AF: 0.387 AC: 1347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs2305220; hg19: chr12-18651702;