12-18510988-C-A

Position:

• chr12-18510988-C-A

Variant summary

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

The NM_001288772.2(PIK3C2G):​c.3323+5527C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,824 control chromosomes in the GnomAD database, including 13,744 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 0.42 (13744 hom., cov: 32)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3C2G	NM_001288772.2	c.3323+5527C>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.3323+5527C>A		intron_variant		5	NM_001288772.2	ENSP00000445381	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63380 AN: 151708 Hom.: 13725 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.418 AC: 63449 AN: 151824 Hom.: 13744 Cov.: 32 AF XY: 0.426 AC XY: 31591 AN XY: 74216

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.381

Alfa AF: 0.376 Hom.: 16966

Bravo AF: 0.417

Asia WGS AF: 0.483 AC: 1681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.49

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: rs10770367; hg19: chr12-18663922;