chr6-43007966-G-C
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_006245.4(PPP2R5D):c.758G>C(p.Arg253Pro) 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R253Q) has been classified as Likely pathogenic.
Frequency
Consequence
NM_006245.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PPP2R5D | NM_006245.4 | c.758G>C | p.Arg253Pro | missense_variant | 7/16 | ENST00000485511.6 | |
PPP2R5D | NM_180976.3 | c.662G>C | p.Arg221Pro | missense_variant | 7/16 | ||
PPP2R5D | NM_180977.3 | c.440G>C | p.Arg147Pro | missense_variant | 5/14 | ||
PPP2R5D | NM_001270476.2 | c.305G>C | p.Arg102Pro | missense_variant | 7/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PPP2R5D | ENST00000485511.6 | c.758G>C | p.Arg253Pro | missense_variant | 7/16 | 1 | NM_006245.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 34
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant classified as Likely pathogenic and reported on 11-09-2017 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 09, 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; Has not been previously published as pathogenic or benign to our knowledge - |
Hogue-Janssens syndrome 1 Pathogenic:1
Pathogenic, no assertion criteria provided | provider interpretation | GenomeConnect - Simons Searchlight | Feb 01, 2019 | Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2019-02-01 and interpreted as Pathogenic. Variant was initially reported on 2018-01-05 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at