Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Myriad Genetics, |
RCV001810469 | SCV002060271 | likely pathogenic | Cockayne syndrome type 2 | 2021-11-16 | criteria provided, single submitter | clinical testing | NM_000124.2(ERCC6):c.2287-2A>G is a canonical splice variant classified as likely pathogenic in the context of ERCC6-related disorders. c.2287-2A>G has been observed in cases with relevant disease (PMID: 19894250, 29572252). Functional assessments of this variant are not available in the literature. c.2287-2A>G has been observed in population frequency databases (gnomAD: NFE 0.003%). In summary, NM_000124.2(ERCC6):c.2287-2A>G is a canonical splice variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |
| Labcorp Genetics |
RCV001855460 | SCV002277945 | likely pathogenic | not provided | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 11 of the ERCC6 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs754978734, gnomAD 0.003%). Disruption of this splice site has been observed in individuals with ERCC6-related conditions (PMID: 19894250, 29572252). ClinVar contains an entry for this variant (Variation ID: 551374). Studies have shown that disruption of this splice site results in skipping of exon 12, but is expected to preserve the integrity of the reading-frame (PMID: 19894250). 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. |
| Fulgent Genetics, |
RCV002477485 | SCV002794367 | pathogenic | DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome type 2; UV-sensitive syndrome 1; Age related macular degeneration 5; Premature ovarian failure 11; Lung cancer | 2022-02-23 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987654 | SCV004804227 | pathogenic | Cockayne syndrome | 2024-01-08 | criteria provided, single submitter | clinical testing | Variant summary: ERCC6 c.2287-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (e.g., Laugel_2010). The variant allele was found at a frequency of 1.2e-05 in 250346 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2287-2A>G has been reported in the literature in both homozygous and compound heterozygous individuals affected with Cockayne Syndrome (e.g., Laugel_2010, Calmels_2018). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 29572252, 19894250). ClinVar contains an entry for this variant (Variation ID: 551374). Based on the evidence outlined above, the variant was classified as pathogenic. |