Variant rs1805076 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_002716.5(PPP2R1B):c.269G>A(p.Gly90Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,614,070 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0069 ( 6 hom., cov: 32)

Exomes 𝑓: 0.011 ( 102 hom. )

Consequence

PPP2R1B
NM_002716.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.53

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP5

Variant 11-111764842-C-T is Pathogenic according to our data. Variant chr11-111764842-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 6621.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-111764842-C-T is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.017846048). . Strength limited to SUPPORTING due to the PP5.

BS2

High AC in GnomAd4 at 1053 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R1B	NM_002716.5 linkuse as main transcript	c.269G>A	p.Gly90Asp	missense_variant	3/15	ENST00000527614.6	NP_002707.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R1B	ENST00000527614.6 linkuse as main transcript	c.269G>A	p.Gly90Asp	missense_variant	3/15	1	NM_002716.5	ENSP00000437193	P2	P30154-1

Frequencies

GnomAD3 genomes

AF:

0.00691

AC:

1052

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00443

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00652

AC:

1638

AN:

251370

Hom.:

AF XY:

0.00676

AC XY:

919

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00389

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.00570

GnomAD4 exome

AF:

0.0109

AC:

15894

AN:

1461774

Hom.:

102

Cov.:

AF XY:

0.0106

AC XY:

7720

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.00188

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00166

Gnomad4 FIN exome

AF:

0.00412

Gnomad4 NFE exome

AF:

0.0134

Gnomad4 OTH exome

AF:

0.00740

GnomAD4 genome

AF:

0.00691

AC:

1053

AN:

152296

Hom.:

Cov.:

AF XY:

0.00655

AC XY:

488

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00443

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00672

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0158

AC:

ESP6500AA

AF:

0.00273

AC:

ESP6500EA

AF:

0.0122

AC:

105

ExAC

AF:

0.00627

AC:

761

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Lung carcinoma

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.0029

.;T;.;.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

D;D;D;T;D

MetaRNN

Benign

0.018

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.94

N;N;N;N;.

MutationTaster

Benign

0.00019

A;A;A;A;A;A

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.98

N;N;N;N;N

REVEL

Benign

0.079

Sift

Benign

0.20

T;T;T;T;T

Sift4G

Benign

0.37

T;T;T;T;T

Polyphen

0.0

B;B;.;.;.

Vest4

0.34

MVP

0.31

MPC

0.28

ClinPred

0.011

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.096

gMVP

0.44

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