rs11044004

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

36 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

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

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

GnomAD2 exomes

AF:

0.386

AC:

95478

AN:

247226

AF XY:

0.384

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 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

African (AFR)

AF:

0.358

AC:

11946

AN:

33356

American (AMR)

AF:

0.393

AC:

17514

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

9683

AN:

26070

East Asian (EAS)

AF:

0.258

AC:

10209

AN:

39646

South Asian (SAS)

AF:

0.342

AC:

29465

AN:

86094

European-Finnish (FIN)

AF:

0.435

AC:

23062

AN:

53064

Middle Eastern (MID)

AF:

0.333

AC:

1916

AN:

5754

European-Non Finnish (NFE)

AF:

0.412

AC:

455371

AN:

1105330

Other (OTH)

AF:

0.386

AC:

23219

AN:

60134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

17272

34543

51815

69086

86358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13908

27816

41724

55632

69540

<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:

0.387

AC:

58817

AN:

151942

Hom.:

11346

Cov.:

AF XY:

0.385

AC XY:

28609

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.357

AC:

14800

AN:

41428

American (AMR)

AF:

0.387

AC:

5899

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1272

AN:

3468

East Asian (EAS)

AF:

0.276

AC:

1425

AN:

5162

South Asian (SAS)

AF:

0.329

AC:

1585

AN:

4814

European-Finnish (FIN)

AF:

0.437

AC:

4613

AN:

10568

Middle Eastern (MID)

AF:

0.325

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.410

AC:

27853

AN:

67946

Other (OTH)

AF:

0.385

AC:

813

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1840

3680

5520

7360

9200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

572

1144

1716

2288

2860

<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:

0.398

Hom.:

39763

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

(source)

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

PhyloP100

0.67

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

PromoterAI

0.015

Neutral

(source)

Varity_R

0.063

gMVP

0.29

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over