chr12-18282440-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001288772.2(PIK3C2G):​c.359C>T​(p.Thr120Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,609,468 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T120K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PIK3C2G
NM_001288772.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.168

Publications

2 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]
RERGL (HGNC:26213): (RERG like) Predicted to enable G protein activity and GTP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.041898847).
BP6
Variant 12-18282440-C-T is Benign according to our data. Variant chr12-18282440-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 4136746.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIK3C2GNM_001288772.2 linkc.359C>T p.Thr120Met 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
PIK3C2GENST00000538779.6 linkc.359C>T p.Thr120Met missense_variant Exon 2 of 33 5 NM_001288772.2 ENSP00000445381.1 F5H369

Frequencies

GnomAD3 genomes
AF:
0.00000673
AC:
1
AN:
148592
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000680
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000201
AC:
5
AN:
248716
AF XY:
0.0000222
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000580
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000167
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460876
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
726778
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.0000447
AC:
2
AN:
44704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26124
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39688
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86240
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53326
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1111196
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60360
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.446
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000673
AC:
1
AN:
148592
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
1
AN XY:
72416
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
40924
American (AMR)
AF:
0.0000680
AC:
1
AN:
14698
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3412
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5116
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4630
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10056
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
310
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
66546
Other (OTH)
AF:
0.00
AC:
0
AN:
2008
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000257
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000248
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
3.3
DANN
Benign
0.28
DEOGEN2
Benign
0.0022
T;.;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.00075
N
LIST_S2
Benign
0.31
T;T;T;.
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.042
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.6
.;.;N;N
PhyloP100
0.17
PrimateAI
Benign
0.26
T
PROVEAN
Benign
1.0
N;N;N;N
REVEL
Benign
0.17
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
0.56
T;T;T;T
Polyphen
0.0
.;B;B;B
Vest4
0.061
MVP
0.39
MPC
0.012
ClinPred
0.021
T
GERP RS
3.5
PromoterAI
-0.010
Neutral
Varity_R
0.014
gMVP
0.16
Mutation Taster
=99/1
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

Publications

Other links and lift over

dbSNP: rs369286185; hg19: chr12-18435374; COSMIC: COSV56815730; COSMIC: COSV56815730; API