rs6779903

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_002718.5(PPP2R3A):c.511G>T(p.Ala171Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,613,636 control chromosomes in the GnomAD database, including 68,852 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 9982 hom., cov: 32)

Exomes 𝑓: 0.28 ( 58870 hom. )

Consequence

PPP2R3A
NM_002718.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.05

Publications

31 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=3.3720255E-5).

BP6

Variant 3-136002009-G-T is Benign according to our data. Variant chr3-136002009-G-T is described in ClinVar as Benign. ClinVar VariationId is 3059643.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002718.5. 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
	PPP2R3A	NM_002718.5	MANE Select	c.511G>T	p.Ala171Ser	missense	Exon 2 of 14	NP_002709.2
	PPP2R3A	NM_001190447.2		c.-213-24823G>T		intron	N/A	NP_001177376.1	Q06190-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP2R3A	ENST00000264977.8	TSL:1 MANE Select	c.511G>T	p.Ala171Ser	missense	Exon 2 of 14	ENSP00000264977.3	Q06190-1
PPP2R3A	ENST00000872859.1		c.511G>T	p.Ala171Ser	missense	Exon 2 of 14	ENSP00000542918.1
PPP2R3A	ENST00000872860.1		c.511G>T	p.Ala171Ser	missense	Exon 2 of 14	ENSP00000542919.1

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52276

AN:

151878

Hom.:

9972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.341

GnomAD2 exomes

AF:

0.294

AC:

73668

AN:

250950

AF XY:

0.289

show subpopulations

Gnomad AFR exome

AF:

0.523

Gnomad AMR exome

AF:

0.304

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.280

AC:

408563

AN:

1461642

Hom.:

58870

Cov.:

AF XY:

0.280

AC XY:

203302

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.529

AC:

17703

AN:

33464

American (AMR)

AF:

0.297

AC:

13279

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

6966

AN:

26132

East Asian (EAS)

AF:

0.227

AC:

9030

AN:

39698

South Asian (SAS)

AF:

0.311

AC:

26827

AN:

86222

European-Finnish (FIN)

AF:

0.316

AC:

16871

AN:

53406

Middle Eastern (MID)

AF:

0.299

AC:

1724

AN:

5768

European-Non Finnish (NFE)

AF:

0.269

AC:

298699

AN:

1111872

Other (OTH)

AF:

0.289

AC:

17464

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

18039

36078

54116

72155

90194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10220

20440

30660

40880

51100

<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:

0.344

AC:

52321

AN:

151994

Hom.:

9982

Cov.:

AF XY:

0.344

AC XY:

25558

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.517

AC:

21434

AN:

41444

American (AMR)

AF:

0.280

AC:

4280

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

930

AN:

3468

East Asian (EAS)

AF:

0.203

AC:

1047

AN:

5170

South Asian (SAS)

AF:

0.324

AC:

1557

AN:

4810

European-Finnish (FIN)

AF:

0.331

AC:

3497

AN:

10568

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18420

AN:

67946

Other (OTH)

AF:

0.343

AC:

721

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1638

3276

4913

6551

8189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<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:

0.288

Hom.:

15395

Bravo

AF:

0.347

TwinsUK

AF:

0.268

AC:

992

ALSPAC

AF:

0.273

AC:

1052

ESP6500AA

AF:

0.506

AC:

2231

ESP6500EA

AF:

0.275

AC:

2364

ExAC

AF:

0.298

AC:

36143

Asia WGS

AF:

0.262

AC:

913

AN:

3478

EpiCase

AF:

0.260

EpiControl

AF:

0.258

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PPP2R3A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.73

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.0038

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.54

MetaRNN

Benign

0.000034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PhyloP100

1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

0.31

REVEL

Benign

0.021

Sift

Benign

0.80

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.022

MPC

0.057

ClinPred

0.00013

GERP RS

0.066

Varity_R

0.041

gMVP

0.077

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over