Variant 8-26354481-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002717.4(PPP2R2A):c.194C>T(p.Ser65Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PPP2R2A
NM_002717.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

PPP2R2A (HGNC:9304): (protein phosphatase 2 regulatory subunit Balpha) The product of this gene belongs to the phosphatase 2 regulatory subunit B family. 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 B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes an alpha isoform of the regulatory subunit B55 subfamily. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

PPP2R2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15216032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2A	NM_002717.4 linkuse as main transcript	c.194C>T	p.Ser65Phe	missense_variant	4/10	ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8 linkuse as main transcript	c.194C>T	p.Ser65Phe	missense_variant	4/10	1	NM_002717.4	P1	P63151-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000443

AC:

AN:

225926

Hom.:

AF XY:

0.00000815

AC XY:

AN XY:

122634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000371

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1397406

Hom.:

Cov.:

AF XY:

0.00000433

AC XY:

AN XY:

692856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2023

The c.224C>T (p.S75F) alteration is located in exon 4 (coding exon 4) of the PPP2R2A gene. This alteration results from a C to T substitution at nucleotide position 224, causing the serine (S) at amino acid position 75 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.51

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

T;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;.

M_CAP

Benign

0.0063

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.26

N;.;.

MutationTaster

Benign

1.0

D;D

PROVEAN

Benign

-1.5

N;N;.

REVEL

Benign

0.054

Sift

Benign

0.036

D;D;.

Sift4G

Benign

0.70

T;T;.

Polyphen

0.0

B;.;.

Vest4

0.34

MutPred

0.38

Loss of disorder (P = 0.0091);.;.;

MVP

0.31

MPC

1.3

ClinPred

0.26

GERP RS

6.0

Varity_R

0.14

gMVP

0.35

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