chr12-18286896-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001288772.2(PIK3C2G):c.728C>T(p.Thr243Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,572,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

PIK3C2G
NM_001288772.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.57

Publications

1 publications found

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:

LOC124902890 (HGNC:):

LOC124902890 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012155741).

BP6

Variant 12-18286896-C-T is Benign according to our data. Variant chr12-18286896-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3888913.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3C2G	NM_001288772.2	MANE Select	c.728C>T	p.Thr243Met	missense	Exon 3 of 33	NP_001275701.1	O75747-1
PIK3C2G	NM_004570.6		c.728C>T	p.Thr243Met	missense	Exon 3 of 32	NP_004561.3	O75747-2
PIK3C2G	NM_001288774.2		c.62C>T	p.Thr21Met	missense	Exon 3 of 33	NP_001275703.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIK3C2G	ENST00000538779.6	TSL:5 MANE Select	c.728C>T	p.Thr243Met	missense	Exon 3 of 33	ENSP00000445381.1	O75747-1
PIK3C2G	ENST00000546003.5	TSL:1	n.*25C>T		non_coding_transcript_exon	Exon 2 of 32	ENSP00000441618.1	F5GWG6
PIK3C2G	ENST00000546003.5	TSL:1	n.*25C>T		3_prime_UTR	Exon 2 of 32	ENSP00000441618.1	F5GWG6

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.0000639

AC:

AN:

203528

AF XY:

0.0000275

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000281

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000556

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000211

AC:

AN:

1420654

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

704302

show subpopulations

African (AFR)

AF:

0.0000622

AC:

AN:

32176

American (AMR)

AF:

0.000229

AC:

AN:

39248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25292

East Asian (EAS)

AF:

0.00

AC:

AN:

38088

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51646

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.0000156

AC:

AN:

1090644

Other (OTH)

AF:

0.0000170

AC:

AN:

58786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41534

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67962

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000145

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000276

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000665

AC:

Asia WGS

AF:

0.00116

AC:

AN:

3472

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.23

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0061

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.62

M_CAP

Benign

0.0024

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

PhyloP100

-1.6

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.21

REVEL

Benign

0.017

Sift

Benign

0.14

Sift4G

Benign

0.12

Polyphen

0.0030

Vest4

0.16

MVP

0.21

MPC

0.012

ClinPred

0.043

GERP RS

-7.8

Varity_R

0.019

gMVP

0.092

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over