Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670772 | SCV000795668 | uncertain significance | DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome type 2 | 2017-11-12 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003558509 | SCV004294365 | pathogenic | not provided | 2023-07-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 532 of the ERCC6 protein (p.Asp532Gly). This variant is present in population databases (rs752712823, gnomAD 0.006%). This missense change has been observed in individual(s) with Cockayne Syndrome (PMID: 25463447). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 555033). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ERCC6 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |