12-18594594-C-A

Variant names:

• chr12-18594594-C-A
• rs11044211
• NM_001288772.2:c.4087+25C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001288772.2(PIK3C2G):​c.4087+25C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000948 in 1,054,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2G	NM_001288772.2	c.4087+25C>A		intron_variant	Intron 30 of 32	ENST00000538779.6	NP_001275701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2G	ENST00000538779.6	c.4087+25C>A		intron_variant	Intron 30 of 32	5	NM_001288772.2	ENSP00000445381.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.48e-7 AC: 1 AN: 1054776 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 532952

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22050

American (AMR) AF: 0.00 AC: 0 AN: 21362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20050

East Asian (EAS) AF: 0.00 AC: 0 AN: 31890

South Asian (SAS) AF: 0.00 AC: 0 AN: 57428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4756

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 801312

Other (OTH) AF: 0.00 AC: 0 AN: 45466

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.96
DANN	Benign	0.17
PhyloP100		0.11

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: rs11044211; hg19: chr12-18747528;