3-136001821-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002718.5(PPP2R3A):c.323A>G(p.Asn108Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00392 in 1,614,154 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N108K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 19 hom. )

Consequence

PPP2R3A
NM_002718.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.11

Publications

11 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=0.0041802824).

BP6

Variant 3-136001821-A-G is Benign according to our data. Variant chr3-136001821-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3038993.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00393 (5740/1461822) while in subpopulation MID AF = 0.0215 (124/5768). AF 95% confidence interval is 0.0184. There are 19 homozygotes in GnomAdExome4. There are 2865 alleles in the male GnomAdExome4 subpopulation. Median coverage is 42. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 gene

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.323A>G	p.Asn108Ser	missense	Exon 2 of 14	NP_002709.2
	PPP2R3A	NM_001190447.2		c.-213-25011A>G		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.323A>G	p.Asn108Ser	missense	Exon 2 of 14	ENSP00000264977.3	Q06190-1
PPP2R3A	ENST00000872859.1		c.323A>G	p.Asn108Ser	missense	Exon 2 of 14	ENSP00000542918.1
PPP2R3A	ENST00000872860.1		c.323A>G	p.Asn108Ser	missense	Exon 2 of 14	ENSP00000542919.1

Frequencies

GnomAD3 genomes

AF:

0.00384

AC:

585

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00510

Gnomad OTH

AF:

0.00907

GnomAD2 exomes

AF:

0.00327

AC:

820

AN:

250578

AF XY:

0.00336

show subpopulations

Gnomad AFR exome

AF:

0.000679

Gnomad AMR exome

AF:

0.00339

Gnomad ASJ exome

AF:

0.00229

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00483

Gnomad OTH exome

AF:

0.00721

GnomAD4 exome

AF:

0.00393

AC:

5740

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

2865

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

33478

American (AMR)

AF:

0.00382

AC:

171

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00222

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00175

AC:

151

AN:

86254

European-Finnish (FIN)

AF:

0.00116

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.0215

AC:

124

AN:

5768

European-Non Finnish (NFE)

AF:

0.00440

AC:

4889

AN:

1111986

Other (OTH)

AF:

0.00411

AC:

248

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

357

714

1071

1428

1785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

174

348

522

696

870

<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:

0.00383

AC:

584

AN:

152332

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

297

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41574

American (AMR)

AF:

0.0107

AC:

164

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00510

AC:

347

AN:

68034

Other (OTH)

AF:

0.00898

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00481

Hom.:

Bravo

AF:

0.00431

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00325

AC:

394

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00589

EpiControl

AF:

0.00688

ClinVar

ClinVar submissions

Significance:Likely 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

0.074

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.15

Eigen_PC

Benign

0.092

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

6.1

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.42

REVEL

Benign

0.076

Sift

Benign

0.87

Sift4G

Benign

1.0

Polyphen

0.058

Vest4

0.32

MVP

0.043

MPC

0.34

ClinPred

0.020

GERP RS

5.8

Varity_R

0.071

gMVP

0.092

Mutation Taster

=87/13

polymorphism

(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