11-64925835-G-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006244.4(PPP2R5B):c.101G>C(p.Arg34Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000456 in 1,601,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

PPP2R5B
NM_006244.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25

Variant links:

Genes affected

PPP2R5B (HGNC:9310): (protein phosphatase 2 regulatory subunit B'beta) The product of this gene belongs to the phosphatase 2A regulatory subunit B family. 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. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a beta isoform of the regulatory subunit B56 subfamily. [provided by RefSeq, Jul 2008]

PPP2R5B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23687363).

BS2

High AC in GnomAdExome4 at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5B	NM_006244.4 link	c.101G>C	p.Arg34Pro	missense_variant	Exon 2 of 14	ENST00000164133.7	NP_006235.1	Q15173-1A0A024R593
PPP2R5B	XM_047427199.1 link	c.101G>C	p.Arg34Pro	missense_variant	Exon 1 of 13		XP_047283155.1
PPP2R5B	XM_011545132.3 link	c.27-13G>C		intron_variant	Intron 2 of 14		XP_011543434.1
PPP2R5B	XM_047427200.1 link	c.27-13G>C		intron_variant	Intron 2 of 14		XP_047283156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP2R5B	ENST00000164133.7 link	c.101G>C	p.Arg34Pro	missense_variant	Exon 2 of 14	1	NM_006244.4	ENSP00000164133.2	Q15173-1
PPP2R5B	ENST00000526559.5 link	c.101G>C	p.Arg34Pro	missense_variant	Exon 2 of 5	5		ENSP00000437088.1	E9PNY3
PPP2R5B	ENST00000532850.1 link	c.-145-13G>C		intron_variant	Intron 1 of 4	3		ENSP00000436136.1	E9PQN5

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000823

AC:

AN:

242982

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

132990

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:

0.0000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000489

AC:

AN:

1451928

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

722128

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:

0.0000614

Gnomad4 OTH exome

AF:

0.0000503

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72960

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000296

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000825

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.101G>C (p.R34P) alteration is located in exon 2 (coding exon 1) of the PPP2R5B gene. This alteration results from a G to C substitution at nucleotide position 101, causing the arginine (R) at amino acid position 34 to be replaced by a proline (P). 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

Uncertain

0.49

BayesDel_addAF

Benign

0.0091

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0095

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

.;M

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.19

Sift

Benign

0.20

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.98

.;D

Vest4

0.40

MutPred

0.22

Loss of MoRF binding (P = 0.0344);Loss of MoRF binding (P = 0.0344);

MVP

0.25

MPC

0.36

ClinPred

0.74

GERP RS

3.7

Varity_R

0.20

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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