3-136001697-G-A

Position:

chr3-136001697-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002718.5(PPP2R3A):c.199G>A(p.Asp67Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,614,080 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D67G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.011 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 21 hom. )

Consequence

PPP2R3A
NM_002718.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.03

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:

PPP2R3A (HGNC:):

PPP2R3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027314126).

BP6

Variant 3-136001697-G-A is Benign according to our data. Variant chr3-136001697-G-A is described in ClinVar as [Benign]. Clinvar id is 3038062.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1647/152282) while in subpopulation AFR AF= 0.0366 (1522/41546). AF 95% confidence interval is 0.0351. There are 25 homozygotes in gnomad4. There are 796 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R3A	NM_002718.5 linkuse as main transcript	c.199G>A	p.Asp67Asn	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 linkuse as main transcript	c.199G>A	p.Asp67Asn	missense_variant	2/14	1	NM_002718.5	ENSP00000264977.3		Q06190-1
PPP2R3A	ENST00000490467.5 linkuse as main transcript	c.-213-25135G>A		intron_variant		2		ENSP00000419344.1		Q06190-3

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1644

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0367

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00318

AC:

798

AN:

251090

Hom.:

AF XY:

0.00242

AC XY:

329

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.00142

AC:

2083

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

958

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0367

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00363

Gnomad4 NFE exome

AF:

0.000407

Gnomad4 OTH exome

AF:

0.00227

GnomAD4 genome

AF:

0.0108

AC:

1647

AN:

152282

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

796

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0366

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00471

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00236

Hom.:

Bravo

AF:

0.0118

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0343

AC:

151

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00388

AC:

471

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPP2R3A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 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

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0044

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.45

REVEL

Benign

0.060

Sift

Benign

0.55

Sift4G

Benign

0.60

Polyphen

0.0030

Vest4

0.19

MVP

0.068

MPC

0.38

ClinPred

0.0081

GERP RS

4.9

Varity_R

0.034

gMVP

0.14

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