Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000763620 | SCV000836840 | pathogenic | GNE myopathy; Sialuria | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr6*) in the GNE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNE are known to be pathogenic (PMID: 24027297). This variant is present in population databases (rs200763627, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with GNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 583405). For these reasons, this variant has been classified as Pathogenic. |
| Eurofins Ntd Llc |
RCV000733643 | SCV000861733 | uncertain significance | not provided | 2018-06-15 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000763620 | SCV000894474 | likely pathogenic | GNE myopathy; Sialuria | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000733643 | SCV002018493 | uncertain significance | not provided | 2022-11-29 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271574 | SCV002555824 | uncertain significance | not specified | 2022-06-10 | criteria provided, single submitter | clinical testing | Variant summary: GNE c.18T>A (p.Tyr6X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. However, an alternative initiation site exists downstream on codon 32 of this variant, which is the canonical initiating codon for other transcripts (e.g. NM_005476). The variant allele was found at a frequency of 0.0002 in 248350 control chromosomes (gnomAD), predominantly at a frequency of 0.0027 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in GNE causing Inclusion Body Myopathy 2 (0.0011), suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.18T>A in individuals affected with Inclusion Body Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters have assessed the variant since 2014: one classified the variant as of uncertain significance, two as likely pathogenic, and one as pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance. |