Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Breda Genetics srl | RCV000449643 | SCV000864412 | pathogenic | Cockayne syndrome type 1 | 2018-01-17 | criteria provided, single submitter | clinical testing | This variant was identified in an individual with Cockayne syndrome type A in the compound heterozygous state with a 80.17 Kbp large deletion encompassing the entire ERCC8 gene on the other allele. This variant is reported with an estimated allele frequency of 0.00006 in gnomAD genomes with no homozygous individuals reported. Shalk et al. detected this variant in the homozygous state in two individuals with Cockayne syndrome, and found that this deep intronic nucleotide change caused the insertion of a cryptic exon in the ERCC8 transcript. These results were validated in vitro with a reporter minigene system (PMID: 29422660). |
Invitae | RCV001861650 | SCV002313559 | likely pathogenic | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 2 of the ERCC8 gene. It does not directly change the encoded amino acid sequence of the ERCC8 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has been observed in individual(s) with Cockayne syndrome (PMID: 29422660). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 397640). Studies have shown that this variant results in the inclusion of 348 nucleotides from intron 2 and introduces a premature termination codon (PMID: 29422660). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Laboratoires de Diagnostic Génétique, |
RCV000449643 | SCV000537862 | pathogenic | Cockayne syndrome type 1 | 2017-03-21 | no assertion criteria provided | research |