ClinVar Miner

Submissions for variant NM_000082.4(ERCC8):c.173+1119G>C

gnomAD frequency: 0.00006  dbSNP: rs1043679457
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Total submissions: 3
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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, Hôpitaux Universitaires de Strasbourg RCV000449643 SCV000537862 pathogenic Cockayne syndrome type 1 2017-03-21 no assertion criteria provided research

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