chr12-18282518-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001288772.2(PIK3C2G):c.437C>T(p.Pro146Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,605,944 control chromosomes in the GnomAD database, including 129,634 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.39 ( 11346 hom., cov: 32)

Exomes 𝑓: 0.40 ( 118288 hom. )

Consequence

PIK3C2G
NM_001288772.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.673

Variant links:

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]

PIK3C2G links:

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

RERGL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001938343).

BP6

Variant 12-18282518-C-T is Benign according to our data. Variant chr12-18282518-C-T is described in ClinVar as [Benign]. Clinvar id is 1297186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2G	NM_001288772.2 link	c.437C>T	p.Pro146Leu	missense_variant	Exon 2 of 33	ENST00000538779.6	NP_001275701.1	O75747F5H369B7ZLY6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2G	ENST00000538779.6 link	c.437C>T	p.Pro146Leu	missense_variant	Exon 2 of 33	5	NM_001288772.2	ENSP00000445381.1		F5H369

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58798

AN:

151824

Hom.:

11343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.358

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.387

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.389

GnomAD3 exomes

AF:

0.386

AC:

95478

AN:

247226

Hom.:

18811

AF XY:

0.384

AC XY:

51580

AN XY:

134264

show subpopulations

Gnomad AFR exome

AF:

0.357

Gnomad AMR exome

AF:

0.394

Gnomad ASJ exome

AF:

0.369

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.387

GnomAD4 exome

AF:

0.401

AC:

582385

AN:

1454002

Hom.:

118288

Cov.:

AF XY:

0.398

AC XY:

288401

AN XY:

723720

show subpopulations

Gnomad4 AFR exome

AF:

0.358

Gnomad4 AMR exome

AF:

0.393

Gnomad4 ASJ exome

AF:

0.371

Gnomad4 EAS exome

AF:

0.258

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.435

Gnomad4 NFE exome

AF:

0.412

Gnomad4 OTH exome

AF:

0.386

GnomAD4 genome

AF:

0.387

AC:

58817

AN:

151942

Hom.:

11346

Cov.:

AF XY:

0.385

AC XY:

28609

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.387

Gnomad4 ASJ

AF:

0.367

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.410

Gnomad4 OTH

AF:

0.385

Alfa

AF:

0.401

Hom.:

29201

Bravo

AF:

0.384

TwinsUK

AF:

0.409

AC:

1517

ALSPAC

AF:

0.412

AC:

1588

ESP6500AA

AF:

0.356

AC:

1290

ESP6500EA

AF:

0.399

AC:

3252

ExAC

AF:

0.385

AC:

46470

Asia WGS

AF:

0.291

AC:

1014

AN:

3478

EpiCase

AF:

0.403

EpiControl

AF:

0.410

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 17991425) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.025

T;.;T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.67

T;T;T;.

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;.;L;L

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.8

D;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.047

D;T;T;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.0030, 0.0020

.;B;B;B

Vest4

0.047

MPC

0.012

ClinPred

0.0076

GERP RS

3.9

Varity_R

0.063

gMVP

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over