rs10841025

Variant names:

• chr12-18426910-C-A
• rs10841025
• NM_001288772.2:c.2504+2871C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288772.2(PIK3C2G):​c.2504+2871C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,084 control chromosomes in the GnomAD database, including 3,956 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 0.22 (3956 hom., cov: 32)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 3 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]

ENSG00000306801 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.331 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2G	NM_001288772.2	MANE Select	c.2504+2871C>A		intron	N/A	NP_001275701.1
	PIK3C2G	NM_004570.6		c.2381+2871C>A		intron	N/A	NP_004561.3
	PIK3C2G	NM_001288774.2		c.1838+2871C>A		intron	N/A	NP_001275703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2G	ENST00000538779.6	TSL:5 MANE Select	c.2504+2871C>A		intron	N/A	ENSP00000445381.1
	PIK3C2G	ENST00000546003.5	TSL:1	n.*1801+2871C>A		intron	N/A	ENSP00000441618.1
	PIK3C2G	ENST00000675017.1		c.2504+2871C>A		intron	N/A	ENSP00000501889.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33668 AN: 151966 Hom.: 3947 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.222 AC: 33720 AN: 152084 Hom.: 3956 Cov.: 32 AF XY: 0.228 AC XY: 16982 AN XY: 74330

African (AFR) AF: 0.221 AC: 9185 AN: 41492

American (AMR) AF: 0.338 AC: 5169 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 654 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1502 AN: 5158

South Asian (SAS) AF: 0.138 AC: 666 AN: 4824

European-Finnish (FIN) AF: 0.283 AC: 2986 AN: 10568

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12888 AN: 67984

Other (OTH) AF: 0.221 AC: 467 AN: 2110

Alfa AF: 0.197 Hom.: 1845

Bravo AF: 0.226

Asia WGS AF: 0.245 AC: 851 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		-0.016
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: rs10841025; hg19: chr12-18579844;