Variant chr12-18648027-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM4BP6BS1BS2

The NM_001288772.2(PIK3C2G):c.4460G>C(p.Ter1487Serext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,581,494 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 14 hom., cov: 32)

Exomes 𝑓: 0.016 ( 234 hom. )

Consequence

PIK3C2G
NM_001288772.2 stop_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

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:

PLCZ1 (HGNC:):

PLCZ1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM4

Stoplost variant in NM_001288772.2 Downstream stopcodon found after 1532 codons.

BP6

Variant 12-18648027-G-C is Benign according to our data. Variant chr12-18648027-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0115 (1749/151858) while in subpopulation NFE AF= 0.0191 (1298/67956). AF 95% confidence interval is 0.0182. There are 14 homozygotes in gnomad4. There are 794 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3C2G	NM_001288772.2 linkuse as main transcript	c.4460G>C	p.Ter1487Serext*?	stop_lost	33/33	ENST00000538779.6	NP_001275701.1	O75747F5H369B7ZLY6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3C2G	ENST00000538779.6 linkuse as main transcript	c.4460G>C	p.Ter1487Serext*?	stop_lost	33/33	5	NM_001288772.2	ENSP00000445381.1		F5H369

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1751

AN:

151738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00296

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00947

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0191

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.0110

AC:

2503

AN:

227776

Hom.:

AF XY:

0.0117

AC XY:

1443

AN XY:

123652

show subpopulations

Gnomad AFR exome

AF:

0.00201

Gnomad AMR exome

AF:

0.00510

Gnomad ASJ exome

AF:

0.00161

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00702

Gnomad FIN exome

AF:

0.0108

Gnomad NFE exome

AF:

0.0174

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

AF:

0.0162

AC:

23134

AN:

1429636

Hom.:

234

Cov.:

AF XY:

0.0161

AC XY:

11450

AN XY:

710982

show subpopulations

Gnomad4 AFR exome

AF:

0.00232

Gnomad4 AMR exome

AF:

0.00522

Gnomad4 ASJ exome

AF:

0.00146

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00774

Gnomad4 FIN exome

AF:

0.0108

Gnomad4 NFE exome

AF:

0.0190

Gnomad4 OTH exome

AF:

0.0130

GnomAD4 genome

AF:

0.0115

AC:

1749

AN:

151858

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

794

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.00295

Gnomad4 AMR

AF:

0.00946

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00643

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.0191

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0111

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0187

AC:

ESP6500AA

AF:

0.00190

AC:

ESP6500EA

AF:

0.0204

AC:

167

ExAC

AF:

0.0111

AC:

1335

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.77

Eigen

Pathogenic

0.81

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.86

Vest4

0.015

GERP RS

3.2

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over