1-204429936-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001377334.1(PIK3C2B):c.4383C>T(p.Pro1461=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 1,607,744 control chromosomes in the GnomAD database, including 9,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1962 hom., cov: 32)

Exomes 𝑓: 0.092 ( 7054 hom. )

Consequence

PIK3C2B
NM_001377334.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00400

Variant links:

Genes affected

PIK3C2B (HGNC:8972): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta) 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. The PI3-kinase activity of this protein is sensitive to low nanomolar levels of the inhibitor wortmanin. The C2 domain of this protein was shown to bind phospholipids but not Ca2+, which suggests that this enzyme may function in a calcium-independent manner. [provided by RefSeq, Jul 2008]

PIK3C2B links:

PPP1R15B-AS1 (HGNC:55838): (PPP1R15B and PIK3C2B antisense RNA 1)

PPP1R15B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 1-204429936-G-A is Benign according to our data. Variant chr1-204429936-G-A is described in ClinVar as [Benign]. Clinvar id is 3060841.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PIK3C2B	NM_001377334.1 linkuse as main transcript	c.4383C>T	p.Pro1461=	synonymous_variant	29/33	ENST00000684373.1
PIK3C2B	NM_002646.4 linkuse as main transcript	c.4383C>T	p.Pro1461=	synonymous_variant	31/35
PIK3C2B	NM_001377335.1 linkuse as main transcript	c.4299C>T	p.Pro1433=	synonymous_variant	32/36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C2B	ENST00000684373.1 linkuse as main transcript	c.4383C>T	p.Pro1461=	synonymous_variant	29/33		NM_001377334.1	P1
PPP1R15B-AS1	ENST00000443515.1 linkuse as main transcript	n.147-5401G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21342

AN:

151922

Hom.:

1941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0983

Gnomad EAS

AF:

0.0793

Gnomad SAS

AF:

0.0485

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0905

Gnomad OTH

AF:

0.119

GnomAD3 exomes

AF:

0.105

AC:

26138

AN:

249946

Hom.:

1732

AF XY:

0.0973

AC XY:

13160

AN XY:

135280

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.137

Gnomad ASJ exome

AF:

0.0856

Gnomad EAS exome

AF:

0.0768

Gnomad SAS exome

AF:

0.0474

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.0875

Gnomad OTH exome

AF:

0.0991

GnomAD4 exome

AF:

0.0918

AC:

133680

AN:

1455704

Hom.:

7054

Cov.:

AF XY:

0.0897

AC XY:

64970

AN XY:

724538

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.0906

Gnomad4 EAS exome

AF:

0.0727

Gnomad4 SAS exome

AF:

0.0467

Gnomad4 FIN exome

AF:

0.142

Gnomad4 NFE exome

AF:

0.0866

Gnomad4 OTH exome

AF:

0.0947

GnomAD4 genome

AF:

0.141

AC:

21391

AN:

152040

Hom.:

1962

Cov.:

AF XY:

0.140

AC XY:

10429

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.0983

Gnomad4 EAS

AF:

0.0795

Gnomad4 SAS

AF:

0.0479

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.0904

Gnomad4 OTH

AF:

0.118

Alfa

AF:

0.0790

Hom.:

209

Bravo

AF:

0.145

Asia WGS

AF:

0.0720

AC:

251

AN:

3478

EpiCase

AF:

0.0840

EpiControl

AF:

0.0797

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PIK3C2B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

Cadd

Benign

7.9

Dann

Benign

0.82

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over