11-111737534-C-G

Position:

chr11-111737534-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000311129.9(PPP2R1B):c.1825G>C(p.Val609Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,614,216 control chromosomes in the GnomAD database, including 1,326 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.028 ( 128 hom., cov: 33)

Exomes 𝑓: 0.037 ( 1198 hom. )

Consequence

PPP2R1B
ENST00000311129.9 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

PPP2R1B (HGNC:9303): (protein phosphatase 2 scaffold subunit Abeta) This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes a beta isoform of the constant regulatory subunit A. Mutations in this gene have been associated with some lung and colon cancers. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

PPP2R1B 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 (MetaRNN=0.0020316243).

BP6

Variant 11-111737534-C-G is Benign according to our data. Variant chr11-111737534-C-G is described in ClinVar as [Benign]. Clinvar id is 3057072.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
PPP2R1B	NM_181699.3 linkuse as main transcript	c.1825G>C	p.Val609Leu	missense_variant	15/16	NP_859050.1
PPP2R1B	NM_181700.2 linkuse as main transcript	c.1633G>C	p.Val545Leu	missense_variant	13/14	NP_859051.1
PPP2R1B	XM_047427196.1 linkuse as main transcript	c.1825G>C	p.Val609Leu	missense_variant	15/16	XP_047283152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	Appris	UniProt
PPP2R1B	ENST00000311129.9 linkuse as main transcript	c.1825G>C	p.Val609Leu	missense_variant	15/16	1	ENSP00000311344	A2	P30154-2
PPP2R1B	ENST00000426998.6 linkuse as main transcript	c.1633G>C	p.Val545Leu	missense_variant	13/14	2	ENSP00000410671		P30154-3
PPP2R1B	ENST00000526287.1 linkuse as main transcript			upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

4326

AN:

152216

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00808

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0806

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0344

Gnomad FIN

AF:

0.0246

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0331

Gnomad OTH

AF:

0.0205

GnomAD3 exomes

AF:

0.0343

AC:

8621

AN:

251466

Hom.:

261

AF XY:

0.0343

AC XY:

4666

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00738

Gnomad AMR exome

AF:

0.0809

Gnomad ASJ exome

AF:

0.00744

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0394

Gnomad FIN exome

AF:

0.0248

Gnomad NFE exome

AF:

0.0322

Gnomad OTH exome

AF:

0.0367

GnomAD4 exome

AF:

0.0365

AC:

53372

AN:

1461882

Hom.:

1198

Cov.:

AF XY:

0.0367

AC XY:

26673

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00517

Gnomad4 AMR exome

AF:

0.0789

Gnomad4 ASJ exome

AF:

0.00658

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0427

Gnomad4 FIN exome

AF:

0.0214

Gnomad4 NFE exome

AF:

0.0383

Gnomad4 OTH exome

AF:

0.0313

GnomAD4 genome

AF:

0.0284

AC:

4326

AN:

152334

Hom.:

128

Cov.:

AF XY:

0.0290

AC XY:

2159

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00806

Gnomad4 AMR

AF:

0.0805

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0348

Gnomad4 FIN

AF:

0.0246

Gnomad4 NFE

AF:

0.0331

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.0304

Hom.:

Bravo

AF:

0.0300

TwinsUK

AF:

0.0429

AC:

159

ALSPAC

AF:

0.0439

AC:

169

ESP6500AA

AF:

0.0129

AC:

ESP6500EA

AF:

0.0350

AC:

301

ExAC

AF:

0.0314

AC:

3818

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0328

EpiControl

AF:

0.0338

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPP2R1B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 18, 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_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.052

Sift

Uncertain

0.017

D;D

Sift4G

Benign

0.091

T;T

Polyphen

0.0

B;.

Vest4

0.064

MutPred

0.23

Loss of methylation at K610 (P = 0.0725);.;

MPC

0.23

ClinPred

0.021

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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