Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV000735981 | SCV000899138 | pathogenic | Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures | 2018-12-10 | criteria provided, single submitter | curation | This variant is interpreted as a Pathogenic for Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1-Moderate => PP1 upgraded in strength to Moderate. PS3-Very Strong => PS3 upgraded in strength to Very Strong (PMID:30401461). |
Genomic Research Center, |
RCV000735981 | SCV000923706 | pathogenic | Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures | 2023-12-10 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics Munich, |
RCV000735981 | SCV001150002 | pathogenic | Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures | 2019-02-14 | criteria provided, single submitter | clinical testing | |
Ce |
RCV002067181 | SCV002496858 | pathogenic | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | ADPRS: PP1:Strong, PM2, PM3, PP4, PS3:Supporting |
3billion, |
RCV000735981 | SCV003841638 | pathogenic | Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.010%). Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product (PMID: 30401461). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.62; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with ADPRS related disorder (PMID: 30401461). The variant has been reported to co-segregate with the disease in at least 5 similarly affected relatives/individuals in the same family or similarly affected unrelated family (PMID: 30401461). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
Neurogenomics Lab, |
RCV000735981 | SCV003930343 | pathogenic | Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures | 2024-05-22 | criteria provided, single submitter | research | PM2_supporting: the highest population allele frequency in gnomAD v4.0 (0.011%; 135/1180056 alleles in European non-Finnish population). PP3 not met: REVEL score is 0.62. PP1_strong: variant segregates with 6 informative meioses across 2 families (PMID 30401461, PMID 34479984). PS3_supporting: functional studies provide supportive evidence that this variant has a damaging effect on the gene or gene product (PMID 30401461, PMID 34479984). PS4 not evaluated as literature probands already counted under PM3. PM3 met: max 1 point awarded for homozygous occurrence of variant in 3 families (PMID: 34479984, PMID 30401461). Sequencing funded by the International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD): https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/. |
OMIM | RCV000735981 | SCV000864180 | pathogenic | Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures | 2019-01-09 | no assertion criteria provided | literature only | |
Solve- |
RCV000735981 | SCV005091407 | likely pathogenic | Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures | 2022-06-01 | no assertion criteria provided | provider interpretation | Variant confirmed as disease-causing by referring clinical team |