1-204427702-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001377334.1(PIK3C2B):c.4533C>T(p.Ser1511=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,613,102 control chromosomes in the GnomAD database, including 9,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1993 hom., cov: 32)

Exomes 𝑓: 0.092 ( 7064 hom. )

Consequence

PIK3C2B
NM_001377334.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.42

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 1-204427702-G-A is Benign according to our data. Variant chr1-204427702-G-A is described in ClinVar as [Benign]. Clinvar id is 3060868.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PIK3C2B	NM_001377334.1 linkuse as main transcript	c.4533C>T	p.Ser1511=	synonymous_variant	31/33	ENST00000684373.1
PIK3C2B	NM_002646.4 linkuse as main transcript	c.4533C>T	p.Ser1511=	synonymous_variant	33/35
PIK3C2B	NM_001377335.1 linkuse as main transcript	c.4449C>T	p.Ser1483=	synonymous_variant	34/36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C2B	ENST00000684373.1 linkuse as main transcript	c.4533C>T	p.Ser1511=	synonymous_variant	31/33		NM_001377334.1	P1
PPP1R15B-AS1	ENST00000443515.1 linkuse as main transcript	n.147-7635G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21307

AN:

152018

Hom.:

1973

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0980

Gnomad EAS

AF:

0.0796

Gnomad SAS

AF:

0.0493

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0905

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.105

AC:

26474

AN:

251456

Hom.:

1804

AF XY:

0.0980

AC XY:

13321

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.0856

Gnomad EAS exome

AF:

0.0770

Gnomad SAS exome

AF:

0.0479

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.0877

Gnomad OTH exome

AF:

0.0990

GnomAD4 exome

AF:

0.0922

AC:

134738

AN:

1460966

Hom.:

7064

Cov.:

AF XY:

0.0900

AC XY:

65442

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.267

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.0904

Gnomad4 EAS exome

AF:

0.0725

Gnomad4 SAS exome

AF:

0.0478

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.0869

Gnomad4 OTH exome

AF:

0.0947

GnomAD4 genome

AF:

0.140

AC:

21357

AN:

152136

Hom.:

1993

Cov.:

AF XY:

0.140

AC XY:

10418

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0980

Gnomad4 EAS

AF:

0.0798

Gnomad4 SAS

AF:

0.0489

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.0905

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.0995

Hom.:

1585

Bravo

AF:

0.144

Asia WGS

AF:

0.0720

AC:

251

AN:

3478

EpiCase

AF:

0.0838

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

-0.49

Cadd

Benign

7.2

Dann

Benign

0.62

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