rs1805076

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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. 14/21 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

Publications

24 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 6621.Status of the report is no_assertion_criteria_provided, 0 stars.

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 rank	MANE	Protein	UniProt
PPP2R1B	NM_002716.5 link	c.269G>A	p.Gly90Asp	missense_variant	Exon 3 of 15	ENST00000527614.6	NP_002707.3	P30154-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R1B	ENST00000527614.6 link	c.269G>A	p.Gly90Asp	missense_variant	Exon 3 of 15	1	NM_002716.5	ENSP00000437193.1		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

GnomAD2 exomes

AF:

0.00652

AC:

1638

AN:

251370

AF XY:

0.00676

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 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

African (AFR)

AF:

0.00197

AC:

AN:

33478

American (AMR)

AF:

0.00206

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00188

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00166

AC:

143

AN:

86256

European-Finnish (FIN)

AF:

0.00412

AC:

220

AN:

53358

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0134

AC:

14862

AN:

1111974

Other (OTH)

AF:

0.00740

AC:

447

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

914

1828

2742

3656

4570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

562

1124

1686

2248

2810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00691

AC:

1053

AN:

152296

Hom.:

Cov.:

AF XY:

0.00655

AC XY:

488

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41564

American (AMR)

AF:

0.00216

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00186

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00443

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0124

AC:

844

AN:

68022

Other (OTH)

AF:

0.00711

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0112

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

Apr 01, 2002

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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;.

PhyloP100

2.5

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

Mutation Taster

=277/23

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over