Variant 3-136002194-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002718.5(PPP2R3A):c.696C>T(p.Cys232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 1,613,220 control chromosomes in the GnomAD database, including 5,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.060 ( 405 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4880 hom. )

Consequence

PPP2R3A
NM_002718.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.221

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 3-136002194-C-T is Benign according to our data. Variant chr3-136002194-C-T is described in ClinVar as [Benign]. Clinvar id is 3038187.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.221 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.082 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R3A	NM_002718.5 linkuse as main transcript	c.696C>T	p.Cys232=	synonymous_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.696C>T	p.Cys232=	synonymous_variant	2/14	1	NM_002718.5	P3	Q06190-1
PPP2R3A	ENST00000490467.5 linkuse as main transcript	c.-213-24638C>T		intron_variant		2			Q06190-3

Frequencies

GnomAD3 genomes

AF:

0.0604

AC:

9183

AN:

152020

Hom.:

404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0303

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0773

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0838

Gnomad OTH

AF:

0.0483

GnomAD3 exomes

AF:

0.0664

AC:

16455

AN:

247968

Hom.:

810

AF XY:

0.0691

AC XY:

9303

AN XY:

134630

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.0219

Gnomad ASJ exome

AF:

0.0448

Gnomad EAS exome

AF:

0.000654

Gnomad SAS exome

AF:

0.0712

Gnomad FIN exome

AF:

0.159

Gnomad NFE exome

AF:

0.0810

Gnomad OTH exome

AF:

0.0656

GnomAD4 exome

AF:

0.0753

AC:

110048

AN:

1461082

Hom.:

4880

Cov.:

AF XY:

0.0758

AC XY:

55126

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.0228

Gnomad4 ASJ exome

AF:

0.0443

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.0759

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.0794

Gnomad4 OTH exome

AF:

0.0665

GnomAD4 genome

AF:

0.0603

AC:

9178

AN:

152138

Hom.:

405

Cov.:

AF XY:

0.0634

AC XY:

4715

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0128

Gnomad4 AMR

AF:

0.0303

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0772

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.0838

Gnomad4 OTH

AF:

0.0478

Alfa

AF:

0.0706

Hom.:

271

Bravo

AF:

0.0460

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.0717

EpiControl

AF:

0.0681

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PPP2R3A-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

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

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.1

DANN

Benign

0.60

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