ClinVar Miner

Submissions for variant NM_017825.3(ADPRS):c.1004T>G (p.Val335Gly)

gnomAD frequency: 0.00011  dbSNP: rs201735454
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Total submissions: 8
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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, Shahid Beheshti University of Medical Sciences 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, Klinikum Rechts Der Isar, TU München RCV000735981 SCV001150002 pathogenic Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures 2019-02-14 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV002067181 SCV002496858 pathogenic not provided 2023-09-01 criteria provided, single submitter clinical testing ADPRS: PP1:Strong, PM2, PM3, PP4, PS3:Supporting
3billion, Medical Genetics 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, Neuroscience Institute, University Of Cape Town 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-RD Consortium 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

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