1-212342260-G-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_006243.4(PPP2R5A):āc.553G>Cā(p.Asp185His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,612,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 32)
Exomes š: 0.00011 ( 0 hom. )
Consequence
PPP2R5A
NM_006243.4 missense
NM_006243.4 missense
Scores
15
2
2
Clinical Significance
Conservation
PhyloP100: 9.80
Genes affected
PPP2R5A (HGNC:9309): (protein phosphatase 2 regulatory subunit B'alpha) 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 an alpha isoform of the regulatory subunit B56 subfamily. Alternative transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.918
BS2
High AC in GnomAd4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP2R5A | NM_006243.4 | c.553G>C | p.Asp185His | missense_variant | 4/13 | ENST00000261461.7 | |
PPP2R5A | NM_001199756.2 | c.382G>C | p.Asp128His | missense_variant | 4/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP2R5A | ENST00000261461.7 | c.553G>C | p.Asp185His | missense_variant | 4/13 | 1 | NM_006243.4 | P1 | |
PPP2R5A | ENST00000537030.3 | c.382G>C | p.Asp128His | missense_variant | 4/13 | 2 | |||
PPP2R5A | ENST00000479259.1 | n.720G>C | non_coding_transcript_exon_variant | 5/5 | 5 | ||||
PPP2R5A | ENST00000498129.6 | n.725G>C | non_coding_transcript_exon_variant | 6/6 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 152058Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000798 AC: 20AN: 250552Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135400
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GnomAD4 exome AF: 0.000109 AC: 159AN: 1460862Hom.: 0 Cov.: 29 AF XY: 0.000124 AC XY: 90AN XY: 726742
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GnomAD4 genome AF: 0.0000855 AC: 13AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74266
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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 | Nov 21, 2022 | The c.553G>C (p.D185H) alteration is located in exon 4 (coding exon 4) of the PPP2R5A gene. This alteration results from a G to C substitution at nucleotide position 553, causing the aspartic acid (D) at amino acid position 185 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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