rs2305220

Variant names:

• chr12-18498768-G-A
• rs2305220
• NM_001288772.2:c.3016+1020G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-18498768-G-A
• chr12-18498768-G-C
• chr12-18498768-G-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.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
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 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.3016+1020G>A		intron	N/A	NP_001275701.1	O75747-1
	PIK3C2G	NM_004570.6		c.2893+1020G>A		intron	N/A	NP_004561.3	O75747-2
	PIK3C2G	NM_001288774.2		c.2350+1020G>A		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.3016+1020G>A		intron	N/A	ENSP00000445381.1	O75747-1
	PIK3C2G	ENST00000546003.5	TSL:1	n.*2313+1020G>A		intron	N/A	ENSP00000441618.1	F5GWG6
	PIK3C2G	ENST00000675017.1		c.3016+1020G>A		intron	N/A	ENSP00000501889.1	O75747-1

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

African (AFR) AF: 0.534 AC: 22103 AN: 41366

American (AMR) AF: 0.381 AC: 5819 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1068 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1760 AN: 5124

South Asian (SAS) AF: 0.429 AC: 2063 AN: 4812

European-Finnish (FIN) AF: 0.302 AC: 3176 AN: 10518

Middle Eastern (MID) AF: 0.331 AC: 96 AN: 290

European-Non Finnish (NFE) AF: 0.354 AC: 24047 AN: 67940

Other (OTH) AF: 0.403 AC: 850 AN: 2110

Alfa AF: 0.371 Hom.: 40364

Bravo AF: 0.415

Asia WGS AF: 0.387 AC: 1347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.46
PhyloP100		0.42
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: rs2305220; hg19: chr12-18651702;