Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001917980 | SCV002171992 | pathogenic | Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q | 2021-03-17 | criteria provided, single submitter | clinical testing | 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. For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with ERCC4-related conditions. 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). This variant is not present in population databases (ExAC no frequency). |
| 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. |