11-64925753-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_006244.4(PPP2R5B):c.19C>T(p.Pro7Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000332 in 1,594,284 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000036 ( 1 hom. )
Consequence
PPP2R5B
NM_006244.4 missense
NM_006244.4 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 5.89
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.06627905).
BS2
High AC in GnomAdExome4 at 52 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP2R5B | NM_006244.4 | c.19C>T | p.Pro7Ser | missense_variant | 2/14 | ENST00000164133.7 | |
PPP2R5B | XM_047427199.1 | c.19C>T | p.Pro7Ser | missense_variant | 1/13 | ||
PPP2R5B | XM_011545132.3 | c.27-95C>T | intron_variant | ||||
PPP2R5B | XM_047427200.1 | c.27-95C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP2R5B | ENST00000164133.7 | c.19C>T | p.Pro7Ser | missense_variant | 2/14 | 1 | NM_006244.4 | P1 | |
PPP2R5B | ENST00000526559.5 | c.19C>T | p.Pro7Ser | missense_variant | 2/5 | 5 | |||
PPP2R5B | ENST00000532850.1 | c.-145-95C>T | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 29
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GnomAD3 exomes AF: 0.0000584 AC: 13AN: 222734Hom.: 0 AF XY: 0.0000653 AC XY: 8AN XY: 122436
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GnomAD4 exome AF: 0.0000361 AC: 52AN: 1442102Hom.: 1 Cov.: 29 AF XY: 0.0000349 AC XY: 25AN XY: 716990
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 29 AF XY: 0.0000134 AC XY: 1AN XY: 74404
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PPP2R5B-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 09, 2023 | The PPP2R5B c.19C>T variant is predicted to result in the amino acid substitution p.Pro7Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.077% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-64693225-C-T), which is more common than expected for a disease gene with a dominant mode of inheritnace, as has been proposed for PPP2R5B. Although we suspect that this variant may be benign, at this time, the clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.91
.;P
Vest4
0.36
MVP
MPC
0.19
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at