Variant chr3-136002243-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002718.5(PPP2R3A):c.745A>G(p.Ile249Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,613,918 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 61 hom. )

Consequence

PPP2R3A
NM_002718.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.94

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008845568).

BP6

Variant 3-136002243-A-G is Benign according to our data. Variant chr3-136002243-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3044322.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R3A	NM_002718.5 linkuse as main transcript	c.745A>G	p.Ile249Val	missense_variant	2/14	ENST00000264977.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R3A	ENST00000264977.8 linkuse as main transcript	c.745A>G	p.Ile249Val	missense_variant	2/14	1	NM_002718.5	P3	Q06190-1
PPP2R3A	ENST00000490467.5 linkuse as main transcript	c.-213-24589A>G		intron_variant		2			Q06190-3

Frequencies

GnomAD3 genomes

AF:

0.00547

AC:

832

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00622

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00951

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00495

AC:

1229

AN:

248292

Hom.:

AF XY:

0.00490

AC XY:

659

AN XY:

134548

show subpopulations

Gnomad AFR exome

AF:

0.00108

Gnomad AMR exome

AF:

0.00192

Gnomad ASJ exome

AF:

0.00210

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000393

Gnomad FIN exome

AF:

0.00610

Gnomad NFE exome

AF:

0.00853

Gnomad OTH exome

AF:

0.00447

GnomAD4 exome

AF:

0.00824

AC:

12049

AN:

1461564

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

5754

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.00646

Gnomad4 NFE exome

AF:

0.00998

Gnomad4 OTH exome

AF:

0.00626

GnomAD4 genome

AF:

0.00546

AC:

832

AN:

152354

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

359

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00622

Gnomad4 NFE

AF:

0.00951

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00793

Hom.:

Bravo

AF:

0.00493

TwinsUK

AF:

0.0135

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0107

AC:

ExAC

AF:

0.00511

AC:

621

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00747

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PPP2R3A-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2019

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

0.26

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0088

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.25

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Benign

0.069

Polyphen

0.99

Vest4

0.45

MVP

0.32

MPC

0.31

ClinPred

0.043

GERP RS

5.2

Varity_R

0.31

gMVP

0.30

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

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