Variant rs114390941 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_StrongBA1

The ENST00000454220.7(PPP2R1A):c.160T>G(p.Phe54Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,469,822 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.018 ( 94 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 54 hom. )

Consequence

PPP2R1A
ENST00000454220.7 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.799

Variant links:

Genes affected

PPP2R1A (HGNC:9302): (protein phosphatase 2 scaffold subunit Aalpha) This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

PPP2R1A links:

PPP2R1A (HGNC:):

PPP2R1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PPP2R1A. . Gene score misZ 4.4565 (greater than the threshold 3.09). Trascript score misZ 4.3877 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, Houge-Janssens syndrome 2, complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024425983).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R1A	NM_014225.6 linkuse as main transcript	c.78+82T>G		intron_variant		ENST00000322088.11	NP_055040.2	P30153A8K7B7
PPP2R1A	NR_033500.2 linkuse as main transcript	n.123+82T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R1A	ENST00000322088.11 linkuse as main transcript	c.78+82T>G		intron_variant		1	NM_014225.6	ENSP00000324804.6		P30153

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2796

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0636

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00634

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.00393

AC:

507

AN:

129066

Hom.:

AF XY:

0.00335

AC XY:

234

AN XY:

69854

show subpopulations

Gnomad AFR exome

AF:

0.0634

Gnomad AMR exome

AF:

0.00288

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000429

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000192

Gnomad OTH exome

AF:

0.00274

GnomAD4 exome

AF:

0.00179

AC:

2353

AN:

1317496

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

1025

AN XY:

651004

show subpopulations

Gnomad4 AFR exome

AF:

0.0616

Gnomad4 AMR exome

AF:

0.00448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000261

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.00476

GnomAD4 genome

AF:

0.0184

AC:

2804

AN:

152326

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1319

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0636

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.0205

ExAC

AF:

0.00435

AC:

141

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.1

PROVEAN

Benign

0.020

REVEL

Benign

0.017

Sift

Benign

0.079

Sift4G

Benign

0.072

MVP

0.57

ClinPred

0.035

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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