Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001040625 | SCV001204210 | pathogenic | not provided | 2023-09-21 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 838966). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Cockayne syndrome (PMID: 29572252). This variant is present in population databases (rs370657735, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Arg268*) in the ERCC8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC8 are known to be pathogenic (PMID: 29572252). |
| Fulgent Genetics, |
RCV002505567 | SCV002810917 | pathogenic | Cockayne syndrome type 1; UV-sensitive syndrome 2 | 2022-01-20 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226423 | SCV003922495 | likely pathogenic | Cockayne syndrome | 2023-03-30 | criteria provided, single submitter | clinical testing | Variant summary: ERCC8 c.802C>T (p.Arg268X) 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. Truncations downstream of this position have been classified as pathogenic in ClinVar. The variant allele was found at a frequency of 4e-06 in 251186 control chromosomes (gnomAD). c.802C>T has been reported in the literature in at least one individual affected with Cockayne Syndrome (Calmels_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite this variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Genomics England Pilot Project, |
RCV001542579 | SCV001760162 | pathogenic | Cockayne syndrome type 1 | no assertion criteria provided | clinical testing |