chr12-18282668-G-T

Variant names:

• chr12-18282668-G-T
• NM_001288772.2:c.587G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001288772.2(PIK3C2G):​c.587G>T​(p.Gly196Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3C2G NM_001288772.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.471
• 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]

RERGL (HGNC:26213): (RERG like) Predicted to enable G protein activity and GTP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15691221).

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.587G>T	p.Gly196Val	missense	Exon 2 of 33	NP_001275701.1	O75747-1
	PIK3C2G	NM_004570.6		c.587G>T	p.Gly196Val	missense	Exon 2 of 32	NP_004561.3	O75747-2
	PIK3C2G	NM_001288774.2		c.-73G>T		5_prime_UTR	Exon 2 of 33	NP_001275703.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2G	ENST00000538779.6	TSL:5 MANE Select	c.587G>T	p.Gly196Val	missense	Exon 2 of 33	ENSP00000445381.1	O75747-1
	PIK3C2G	ENST00000546003.5	TSL:1	n.587G>T		non_coding_transcript_exon	Exon 1 of 32	ENSP00000441618.1	F5GWG6
	PIK3C2G	ENST00000675017.1		c.587G>T	p.Gly196Val	missense	Exon 2 of 33	ENSP00000501889.1	O75747-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.47
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.078
Sift	Benign	0.051	T
Sift4G	Benign	0.19	T
Polyphen		0.88	P
Vest4		0.11
MutPred		0.48		Gain of catalytic residue at N199 (P = 0.0047)
MVP		0.66
MPC		0.020
ClinPred		0.49	T
GERP RS		0.15
PromoterAI		-0.032	Neutral
Varity_R		0.079
gMVP		0.20
Mutation Taster		=98/2	polymorphism

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

hg19: chr12-18435602;