12-18594453-A-T

Variant names:

• chr12-18594453-A-T
• rs12827507
• NM_001288772.2:c.4012-41A>T

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.4012-41A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,093,100 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: 9.1e-7 (0 hom.)
• Consequence: PIK3C2G NM_001288772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• 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=-0.92).

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.4012-41A>T		intron	N/A	NP_001275701.1
	PIK3C2G	NM_004570.6		c.3889-41A>T		intron	N/A	NP_004561.3
	PIK3C2G	NM_001288774.2		c.3346-41A>T		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.4012-41A>T		intron	N/A	ENSP00000445381.1
	PIK3C2G	ENST00000546003.5	TSL:1	n.*3309-41A>T		intron	N/A	ENSP00000441618.1
	PIK3C2G	ENST00000675017.1		c.4012-41A>T		intron	N/A	ENSP00000501889.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1093100 Hom.: 0 Cov.: 14 AF XY: 0.00000180 AC XY: 1 AN XY: 556190

African (AFR) AF: 0.00 AC: 0 AN: 22132

American (AMR) AF: 0.00 AC: 0 AN: 25674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21982

East Asian (EAS) AF: 0.00 AC: 0 AN: 33434

South Asian (SAS) AF: 0.00 AC: 0 AN: 65022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4576

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 821522

Other (OTH) AF: 0.0000211 AC: 1 AN: 47330

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.37
PhyloP100		-0.29

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: rs12827507; hg19: chr12-18747387;