dbSNP rs747411292: PPP2R5B:p.Ser161Trp (chr11-64927887-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006244.4(PPP2R5B):c.482C>G(p.Ser161Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S161L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PPP2R5B
NM_006244.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.82

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5B	NM_006244.4 link	c.482C>G	p.Ser161Trp	missense_variant	Exon 4 of 14	ENST00000164133.7	NP_006235.1	Q15173-1A0A024R593
PPP2R5B	XM_047427199.1 link	c.482C>G	p.Ser161Trp	missense_variant	Exon 3 of 13		XP_047283155.1
PPP2R5B	XM_011545132.3 link	c.395C>G	p.Ser132Trp	missense_variant	Exon 5 of 15		XP_011543434.1
PPP2R5B	XM_047427200.1 link	c.395C>G	p.Ser132Trp	missense_variant	Exon 5 of 15		XP_047283156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP2R5B	ENST00000164133.7 link	c.482C>G	p.Ser161Trp	missense_variant	Exon 4 of 14	1	NM_006244.4	ENSP00000164133.2	Q15173-1
PPP2R5B	ENST00000526559.5 link	c.482C>G	p.Ser161Trp	missense_variant	Exon 4 of 5	5		ENSP00000437088.1	E9PNY3
PPP2R5B	ENST00000532850.1 link	c.224C>G	p.Ser75Trp	missense_variant	Exon 4 of 5	3		ENSP00000436136.1	E9PQN5
PPP2R5B	ENST00000528530.1 link	n.154C>G		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455630

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33338

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86094

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106382

Other (OTH)

AF:

0.00

AC:

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.82

D;D;D

Eigen

Pathogenic

0.78

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Uncertain

0.22

MutationAssessor

Pathogenic

3.3

.;M;.

PhyloP100

7.8

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-5.6

D;D;D

REVEL

Pathogenic

0.81

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.61

MutPred

0.54

Gain of catalytic residue at S161 (P = 0);Gain of catalytic residue at S161 (P = 0);.;

MVP

0.51

MPC

2.5

ClinPred

1.0

GERP RS

3.5

Varity_R

0.82

gMVP

0.76

Mutation Taster

=32/68

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over