rs9814557

Variant names:

Variant summary

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

The NM_002718.5(PPP2R3A):c.200A>G(p.Asp67Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,613,762 control chromosomes in the GnomAD database, including 73,912 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 Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D67N) has been classified as Benign.

Frequency

Genomes: 𝑓 0.23 ( 4882 hom., cov: 32)

Exomes 𝑓: 0.30 ( 69030 hom. )

Consequence

PPP2R3A
NM_002718.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.33

Publications

38 publications found

Variant links:

Genes affected

PPP2R3A (HGNC:9307): (protein phosphatase 2 regulatory subunit B''alpha) This gene encodes one of the regulatory subunits of the protein phosphatase 2. Protein phosphatase 2 (formerly named type 2A) is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2 holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B''/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B'' family. The B'' family has been further divided into subfamilies. The product of this gene belongs to the alpha subfamily of regulatory subunit B''. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Jun 2010]

PPP2R3A 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=0.0041641295).

BP6

Variant 3-136001698-A-G is Benign according to our data. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001698-A-G is described in CliVar as Benign. Clinvar id is 3055861.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R3A	NM_002718.5 link	c.200A>G	p.Asp67Gly	missense_variant	Exon 2 of 14	ENST00000264977.8	NP_002709.2	Q06190-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R3A	ENST00000264977.8 link	c.200A>G	p.Asp67Gly	missense_variant	Exon 2 of 14	1	NM_002718.5	ENSP00000264977.3		Q06190-1
PPP2R3A	ENST00000490467.5 link	c.-213-25134A>G		intron_variant	Intron 1 of 12	2		ENSP00000419344.1		Q06190-3

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35137

AN:

152010

Hom.:

4885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.252

AC:

63197

AN:

250856

AF XY:

0.264

show subpopulations

Gnomad AFR exome

AF:

0.0966

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.0218

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.320

Gnomad OTH exome

AF:

0.277

GnomAD4 exome

AF:

0.299

AC:

436365

AN:

1461634

Hom.:

69030

Cov.:

AF XY:

0.300

AC XY:

218463

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.0924

AC:

3093

AN:

33478

American (AMR)

AF:

0.140

AC:

6271

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

8946

AN:

26134

East Asian (EAS)

AF:

0.0194

AC:

770

AN:

39698

South Asian (SAS)

AF:

0.294

AC:

25341

AN:

86248

European-Finnish (FIN)

AF:

0.296

AC:

15807

AN:

53390

Middle Eastern (MID)

AF:

0.297

AC:

1715

AN:

5768

European-Non Finnish (NFE)

AF:

0.321

AC:

357344

AN:

1111842

Other (OTH)

AF:

0.283

AC:

17078

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

17946

35893

53839

71786

89732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11362

22724

34086

45448

56810

<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:

0.231

AC:

35131

AN:

152128

Hom.:

4882

Cov.:

AF XY:

0.229

AC XY:

17047

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.101

AC:

4177

AN:

41530

American (AMR)

AF:

0.189

AC:

2890

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1201

AN:

3468

East Asian (EAS)

AF:

0.0237

AC:

123

AN:

5186

South Asian (SAS)

AF:

0.261

AC:

1258

AN:

4826

European-Finnish (FIN)

AF:

0.290

AC:

3062

AN:

10552

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.318

AC:

21599

AN:

67980

Other (OTH)

AF:

0.229

AC:

483

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1330

2660

3991

5321

6651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.287

Hom.:

24813

Bravo

AF:

0.217

TwinsUK

AF:

0.320

AC:

1186

ALSPAC

AF:

0.338

AC:

1301

ESP6500AA

AF:

0.102

AC:

448

ESP6500EA

AF:

0.313

AC:

2694

ExAC

AF:

0.254

AC:

30793

Asia WGS

AF:

0.140

AC:

488

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPP2R3A-related disorder

Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

PhyloP100

3.3

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.2

REVEL

Benign

0.042

Sift

Uncertain

0.013

Sift4G

Benign

0.12

Polyphen

0.085

Vest4

0.11

MPC

0.43

ClinPred

0.023

GERP RS

3.3

Varity_R

0.12

gMVP

0.22

Mutation Taster

=96/4

polymorphism (auto)

(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