11-111737534-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_181699.3(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. 13/18 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
NM_181699.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.09

Publications

12 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: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181699.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R1B	NM_181699.3		c.1825G>C	p.Val609Leu	missense	Exon 15 of 16	NP_859050.1	P30154-2
	PPP2R1B	NM_181700.2		c.1633G>C	p.Val545Leu	missense	Exon 13 of 14	NP_859051.1	P30154-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP2R1B	ENST00000311129.9	TSL:1	c.1825G>C	p.Val609Leu	missense	Exon 15 of 16	ENSP00000311344.5	P30154-2
PPP2R1B	ENST00000426998.6	TSL:2	c.1633G>C	p.Val545Leu	missense	Exon 13 of 14	ENSP00000410671.2	P30154-3
PPP2R1B	ENST00000526287.1	TSL:1	n.-31G>C		upstream_gene	N/A

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

GnomAD2 exomes

AF:

0.0343

AC:

8621

AN:

251466

AF XY:

0.0343

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 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

African (AFR)

AF:

0.00517

AC:

173

AN:

33480

American (AMR)

AF:

0.0789

AC:

3527

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00658

AC:

172

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0427

AC:

3679

AN:

86256

European-Finnish (FIN)

AF:

0.0214

AC:

1144

AN:

53420

Middle Eastern (MID)

AF:

0.0281

AC:

162

AN:

5768

European-Non Finnish (NFE)

AF:

0.0383

AC:

42617

AN:

1112008

Other (OTH)

AF:

0.0313

AC:

1893

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

3034

6068

9102

12136

15170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1674

3348

5022

6696

8370

<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:

0.0284

AC:

4326

AN:

152334

Hom.:

128

Cov.:

AF XY:

0.0290

AC XY:

2159

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00806

AC:

335

AN:

41586

American (AMR)

AF:

0.0805

AC:

1231

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5186

South Asian (SAS)

AF:

0.0348

AC:

168

AN:

4828

European-Finnish (FIN)

AF:

0.0246

AC:

261

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0331

AC:

2254

AN:

68024

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

219

437

656

874

1093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0304

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

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PPP2R1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.1

PhyloP100

1.1

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.27

REVEL

Benign

0.052

Sift

Uncertain

0.017

Sift4G

Benign

0.091

Polyphen

0.0

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

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over