dbSNP rs753832506: PPP2CB:p.Gln162Arg (chr8-30797582-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001009552.2(PPP2CB):c.485A>G(p.Gln162Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PPP2CB
NM_001009552.2 missense, splice_region

Scores

Splicing: ADA: 0.9969

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Variant links:

Genes affected

PPP2CB (HGNC:9300): (protein phosphatase 2 catalytic subunit beta) This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A 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. This gene encodes a beta isoform of the catalytic subunit. [provided by RefSeq, Mar 2010]

PPP2CB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2CB	NM_001009552.2 link	c.485A>G	p.Gln162Arg	missense_variant, splice_region_variant	Exon 3 of 7	ENST00000221138.9	NP_001009552.1	P62714A0A140VJS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP2CB	ENST00000221138.9 link	c.485A>G	p.Gln162Arg	missense_variant, splice_region_variant	Exon 3 of 7	1	NM_001009552.2	ENSP00000221138.4	P62714
PPP2CB	ENST00000518243.5 link	c.344A>G	p.Gln115Arg	missense_variant, splice_region_variant	Exon 3 of 5	3		ENSP00000428618.1	E5RHC1
PPP2CB	ENST00000520056.1 link	c.290A>G	p.Gln97Arg	missense_variant, splice_region_variant	Exon 3 of 4	5		ENSP00000428866.1	E5RFI3
PPP2CB	ENST00000518564.1 link	c.141+2135A>G		intron_variant	Intron 2 of 2	3		ENSP00000428142.1	E5RJX4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250444

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458812

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725940

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000451

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.485A>G (p.Q162R) alteration is located in exon 3 (coding exon 3) of the PPP2CB gene. This alteration results from a A to G substitution at nucleotide position 485, causing the glutamine (Q) at amino acid position 162 to be replaced by an arginine (R). 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

0.20

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

D;.;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.090

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-0.55

N;.;.

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.84

MutPred

0.40

Loss of catalytic residue at C165 (P = 0.2804);.;.;

MVP

0.81

MPC

1.8

ClinPred

0.69

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.010

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