chr3-136001730-G-A

Position:

chr3-136001730-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002718.5(PPP2R3A):c.232G>A(p.Gly78Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,614,088 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 21 hom. )

Consequence

PPP2R3A
NM_002718.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.16

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047598183).

BP6

Variant 3-136001730-G-A is Benign according to our data. Variant chr3-136001730-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3034364.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-136001730-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R3A	NM_002718.5 link	c.232G>A	p.Gly78Arg	missense_variant	2/14	ENST00000264977.8	NP_002709.2	Q06190-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R3A	ENST00000264977.8 link	c.232G>A	p.Gly78Arg	missense_variant	2/14	1	NM_002718.5	ENSP00000264977.3		Q06190-1
PPP2R3A	ENST00000490467.5 link	c.-213-25102G>A		intron_variant		2		ENSP00000419344.1		Q06190-3

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

416

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00484

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00277

AC:

696

AN:

250952

Hom.:

AF XY:

0.00303

AC XY:

411

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00238

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00500

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00452

AC:

6604

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

3225

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.000880

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.00552

Gnomad4 OTH exome

AF:

0.00351

GnomAD4 genome

AF:

0.00273

AC:

416

AN:

152294

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00484

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00500

Hom.:

Bravo

AF:

0.00273

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00260

AC:

315

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPP2R3A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 31, 2022

This variant is classified as likely 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

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

M_CAP

Benign

0.033

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.2

REVEL

Benign

0.21

Sift

Uncertain

0.0030

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.27

MutPred

0.42

Gain of phosphorylation at S81 (P = 0.0817);

MVP

0.13

MPC

0.41

ClinPred

0.026

GERP RS

5.8

Varity_R

0.16

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over