NM_001288772.2:c.22G>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001288772.2(PIK3C2G):c.22G>T(p.Asp8Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 1,600,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

PIK3C2G
NM_001288772.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021481186).

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.22G>T	p.Asp8Tyr	missense	Exon 2 of 33	NP_001275701.1	O75747-1
PIK3C2G	NM_004570.6		c.22G>T	p.Asp8Tyr	missense	Exon 2 of 32	NP_004561.3	O75747-2
PIK3C2G	NM_001288774.2		c.-638G>T		5_prime_UTR	Exon 2 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.22G>T	p.Asp8Tyr	missense	Exon 2 of 33	ENSP00000445381.1	O75747-1
PIK3C2G	ENST00000546003.5	TSL:1	n.22G>T		non_coding_transcript_exon	Exon 1 of 32	ENSP00000441618.1	F5GWG6
PIK3C2G	ENST00000675017.1		c.22G>T	p.Asp8Tyr	missense	Exon 2 of 33	ENSP00000501889.1	O75747-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

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:

0.000144

AC:

AN:

229684

AF XY:

0.000145

show subpopulations

Gnomad AFR exome

AF:

0.0000710

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00168

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000195

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1448146

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

719006

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33258

American (AMR)

AF:

0.00

AC:

AN:

42448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25782

East Asian (EAS)

AF:

0.000712

AC:

AN:

39344

South Asian (SAS)

AF:

0.00

AC:

AN:

84540

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000453

AC:

AN:

1104278

Other (OTH)

AF:

0.000117

AC:

AN:

59940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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:

0.000138

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41506

American (AMR)

AF:

0.0000655

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00212

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

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:

0.0000757

Hom.:

Bravo

AF:

0.000128

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000829

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.086

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Benign

0.12

Eigen_PC

Benign

0.076

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.81

M_CAP

Benign

0.035

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.8

PhyloP100

2.3

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

REVEL

Benign

0.20

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0030

Polyphen

0.97

Vest4

0.62

MVP

0.79

MPC

0.064

ClinPred

0.11

GERP RS

3.4

Varity_R

0.10

gMVP

0.47

Mutation Taster

=93/7

polymorphism

(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

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