Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000822020 | SCV000962800 | pathogenic | Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q | 2023-06-21 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this premature translational stop signal affects ERCC4 function (PMID: 24412486). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Arg799 amino acid residue in ERCC4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8797827, 9579555, 20221251, 23623389, 26074087, 29403087, 29892709). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 664022). This premature translational stop signal has been observed in individual(s) with giant cell tumor of the bone and in an individual with alveolar rhabdomyosarcoma (PMID: 28878254). This variant is present in population databases (rs2020959, gnomAD 0.04%). This sequence change creates a premature translational stop signal (p.Cys723*) in the ERCC4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 194 amino acid(s) of the ERCC4 protein. |
| Leiden Open Variation Database | RCV001194781 | SCV001364567 | uncertain significance | not provided | 2017-03-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Gerard C.P. Schaafsma. |