rs17197552

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.1924A>G(p.Ser642Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,613,444 control chromosomes in the GnomAD database, including 75,959 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).

Frequency

Genomes: 𝑓 0.25 ( 5414 hom., cov: 32)

Exomes 𝑓: 0.30 ( 70545 hom. )

Consequence

PPP2R3A
NM_002718.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.36

Publications

36 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=0.0038633943).

BP6

Variant 3-136003422-A-G is Benign according to our data. Variant chr3-136003422-A-G is described in ClinVar as Benign. ClinVar VariationId is 3056776.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R3A	NM_002718.5 link	c.1924A>G	p.Ser642Gly	missense_variant	Exon 2 of 14	ENST00000264977.8	NP_002709.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R3A	ENST00000264977.8 link	c.1924A>G	p.Ser642Gly	missense_variant	Exon 2 of 14	1	NM_002718.5	ENSP00000264977.3
PPP2R3A	ENST00000490467.5 link	c.-213-23410A>G		intron_variant	Intron 1 of 12	2		ENSP00000419344.1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38640

AN:

151974

Hom.:

5417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.196

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.240

GnomAD2 exomes

AF:

0.262

AC:

65660

AN:

250754

AF XY:

0.274

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.0230

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.303

AC:

442857

AN:

1461352

Hom.:

70545

Cov.:

AF XY:

0.305

AC XY:

222024

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.170

AC:

5692

AN:

33456

American (AMR)

AF:

0.144

AC:

6436

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

8990

AN:

26102

East Asian (EAS)

AF:

0.0201

AC:

799

AN:

39690

South Asian (SAS)

AF:

0.317

AC:

27296

AN:

86220

European-Finnish (FIN)

AF:

0.300

AC:

16006

AN:

53406

Middle Eastern (MID)

AF:

0.309

AC:

1781

AN:

5768

European-Non Finnish (NFE)

AF:

0.322

AC:

358293

AN:

1111632

Other (OTH)

AF:

0.291

AC:

17564

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

16745

33491

50236

66982

83727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11430

22860

34290

45720

57150

<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:

0.254

AC:

38652

AN:

152092

Hom.:

5414

Cov.:

AF XY:

0.253

AC XY:

18777

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.176

AC:

7296

AN:

41500

American (AMR)

AF:

0.196

AC:

2998

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1205

AN:

3470

East Asian (EAS)

AF:

0.0255

AC:

132

AN:

5182

South Asian (SAS)

AF:

0.283

AC:

1365

AN:

4816

European-Finnish (FIN)

AF:

0.295

AC:

3115

AN:

10570

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21692

AN:

67958

Other (OTH)

AF:

0.240

AC:

506

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1429

2859

4288

5718

7147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.296

Hom.:

28831

Bravo

AF:

0.243

TwinsUK

AF:

0.320

AC:

1186

ALSPAC

AF:

0.339

AC:

1307

ESP6500AA

AF:

0.175

AC:

770

ESP6500EA

AF:

0.315

AC:

2708

ExAC

AF:

0.265

AC:

32217

Asia WGS

AF:

0.165

AC:

577

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPP2R3A-related disorder

Benign:1

Jul 02, 2020

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

0.063

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.0

PhyloP100

2.4

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.080

REVEL

Benign

0.033

Sift

Benign

0.16

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.013

MPC

0.057

ClinPred

0.0068

GERP RS

3.5

Varity_R

0.051

gMVP

0.27

Mutation Taster

=99/1

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