Variant 11-64926835-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006244.4(PPP2R5B):c.323A>G(p.Asn108Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PPP2R5B
NM_006244.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PPP2R5B	NM_006244.4 linkuse as main transcript	c.323A>G	p.Asn108Ser	missense_variant	3/14	ENST00000164133.7
PPP2R5B	XM_047427199.1 linkuse as main transcript	c.323A>G	p.Asn108Ser	missense_variant	2/13
PPP2R5B	XM_011545132.3 linkuse as main transcript	c.236A>G	p.Asn79Ser	missense_variant	4/15
PPP2R5B	XM_047427200.1 linkuse as main transcript	c.236A>G	p.Asn79Ser	missense_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R5B	ENST00000164133.7 linkuse as main transcript	c.323A>G	p.Asn108Ser	missense_variant	3/14	1	NM_006244.4	P1	Q15173-1
PPP2R5B	ENST00000526559.5 linkuse as main transcript	c.323A>G	p.Asn108Ser	missense_variant	3/5	5
PPP2R5B	ENST00000532850.1 linkuse as main transcript	c.65A>G	p.Asn22Ser	missense_variant	3/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727244

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

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

May 18, 2022

The c.323A>G (p.N108S) alteration is located in exon 3 (coding exon 2) of the PPP2R5B gene. This alteration results from a A to G substitution at nucleotide position 323, causing the asparagine (N) at amino acid position 108 to be replaced by a serine (S). 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

0.087

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

D;D;D

Eigen

Benign

0.014

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Benign

-0.85

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Benign

0.10

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.53

T;T;T

Polyphen

0.11

.;B;.

Vest4

0.63

MutPred

0.48

Gain of disorder (P = 0.0696);Gain of disorder (P = 0.0696);.;

MVP

0.55

MPC

1.9

ClinPred

0.95

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.39

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over