rs863225081
Variant summary
Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PM1PM2PM5PP2PP3_ModeratePP5_Very_Strong
The ENST00000485511.6(PPP2R5D):c.589G>A(p.Glu197Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E197G) has been classified as Likely pathogenic.
Frequency
Consequence
ENST00000485511.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PPP2R5D | NM_006245.4 | c.589G>A | p.Glu197Lys | missense_variant | 5/16 | ENST00000485511.6 | NP_006236.1 | |
PPP2R5D | NM_180976.3 | c.493G>A | p.Glu165Lys | missense_variant | 5/16 | NP_851307.1 | ||
PPP2R5D | NM_180977.3 | c.271G>A | p.Glu91Lys | missense_variant | 3/14 | NP_851308.1 | ||
PPP2R5D | NM_001270476.2 | c.136G>A | p.Glu46Lys | missense_variant | 5/16 | NP_001257405.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PPP2R5D | ENST00000485511.6 | c.589G>A | p.Glu197Lys | missense_variant | 5/16 | 1 | NM_006245.4 | ENSP00000417963 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hogue-Janssens syndrome 1 Pathogenic:1Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Likely pathogenic, no assertion criteria provided | provider interpretation | GenomeConnect - Simons Searchlight | Dec 15, 2017 | Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-12-15 and interpreted as Likely Pathogenic. Variant was initially reported on 2015-06-04 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 14, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26576547, 30676711, 34448180, 32074998) - |
PPP2R5D-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 29, 2023 | The PPP2R5D c.589G>A variant is predicted to result in the amino acid substitution p.Glu197Lys. This variant was reported, de novo, in an individual with developmental delays, intellectual disability, macrocephaly, hypotonia, congenital scoliosis and mild dysmorphic features (Shang et al. 2016. PubMed ID: 26576547). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at