Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion, |
RCV002251596 | SCV002521516 | likely pathogenic | Familial juvenile hyperuricemic nephropathy type 1 | 2024-07-30 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v4.0.0 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.69 (>=0.6); 3Cnet: 0.79 (>=0.6)]. The same nucleotide change resulting in the same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV001344662 / PMID: 21060763). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Ce |
RCV003222351 | SCV003917499 | likely pathogenic | not provided | 2023-01-01 | criteria provided, single submitter | clinical testing | UMOD: PM2, PP2, PP3, PP4, PS4:Supporting |
| Molecular Genetics, |
RCV005250201 | SCV005900500 | likely pathogenic | Autosomal dominant medullary cystic kidney disease with or without hyperuricemia | 2024-11-04 | criteria provided, single submitter | clinical testing | This sequence change in UMOD is predicted to replace alanine with glutamic acid at codon 461, p.(Ala461Glu). The alanine residue is highly conserved (100 vertebrates, Multiz Alignments), and is located in the zona pellucida-like (ZP) domain. There is a large physicochemical difference between alanine and glutamic acid. This variant is absent from the population database gnomAD v4.1. This variant has been reported in at least four unrelated probands with UMOD-related tubulointerstitial kidney disease and segregates with disease in two families (PMID: 21060763; 21868615; 31509055; 32450155; ClinVar: SCV003917499.13). Computational evidence predicts a deleterious effect for the missense substitution (REVEL = 0.691) and predicts no impact on splicing (SpliceAI) for the nucleotide change. Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.7.0, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PM2_Supporting, PP1, PP3, PS4 |
| Yale Center for Mendelian Genomics, |
RCV002251596 | SCV002106609 | likely pathogenic | Familial juvenile hyperuricemic nephropathy type 1 | 2019-02-14 | no assertion criteria provided | literature only |