Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001917980 | SCV002171992 | pathogenic | Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q | 2021-03-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with ERCC4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe186Cysfs*24) in the ERCC4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC4 are known to be pathogenic (PMID: 9580660). |
| Clinical Genomics Laboratory, |
RCV004555891 | SCV005045029 | likely pathogenic | Xeroderma pigmentosum, group F | 2023-12-21 | criteria provided, single submitter | clinical testing | The ERCC4 c.557_558del (p.Phe186CysfsTer24) variant, to our knowledge, has not been reported in the medical literature but has been reported in the ClinVar database as a germline pathogenic variant by one submitter. This variant is only observed on 1/251,444 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant causes a frameshift by deleting two nucleotides, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely pathogenic. |