12-18282452-G-T

Variant names:

• chr12-18282452-G-T
• rs761165027
• NM_001288772.2:c.371G>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.371G>T​(p.Cys124Phe) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C124Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3C2G NM_001288772.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463
• 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=0.08448678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2G	NM_001288772.2	c.371G>T	p.Cys124Phe	missense_variant	Exon 2 of 33	ENST00000538779.6	NP_001275701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2G	ENST00000538779.6	c.371G>T	p.Cys124Phe	missense_variant	Exon 2 of 33	5	NM_001288772.2	ENSP00000445381.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.68
DANN	Benign	0.94
DEOGEN2	Benign	0.0069	T;.;T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.68	T;T;T;.
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.084	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	.;.;L;L
PhyloP100		0.46
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.21	N;N;N;N
REVEL	Benign	0.033
Sift	Uncertain	0.026	D;D;D;D
Sift4G	Uncertain	0.030	D;D;D;D
Polyphen		0.19, 0.12	.;B;B;B
Vest4		0.11
MutPred		0.23		Gain of catalytic residue at P129 (P = 0.0027);Gain of catalytic residue at P129 (P = 0.0027);Gain of catalytic residue at P129 (P = 0.0027);Gain of catalytic residue at P129 (P = 0.0027);
MVP		0.46
MPC		0.014
ClinPred		0.14	T
GERP RS		2.9
PromoterAI		0.013	Neutral
Varity_R		0.098
gMVP		0.17
Mutation Taster		=95/5	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

dbSNP: rs761165027; hg19: chr12-18435386;