Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000673212 | SCV000798390 | likely pathogenic | Wilson disease | 2018-03-08 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000673212 | SCV001139352 | pathogenic | Wilson disease | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000673212 | SCV001482032 | pathogenic | Wilson disease | 2021-02-20 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.3061-12T>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a canonical 3' acceptor site. Two predict the variant weakens a canonical 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (Loudianos_2002). The variant allele was found at a frequency of 4.1e-06 in 245682 control chromosomes. c.3061-12T>A has been reported in the literature in multiple individuals affected with Wilson Disease (example, Loudianos_2012, Silva_2011, Bost_2012, Dufernez_2013, Sanchez-Monteagudo_2020). These data indicate that the variant is very likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. One submitter has cited overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV000673212 | SCV001590618 | pathogenic | Wilson disease | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 13 of the ATP7B gene. It does not directly change the encoded amino acid sequence of the ATP7B protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individual(s) with Wilson disease (PMID: 12325021, 22687675, 23567103). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 557116). Studies have shown that this variant results in skipping of exon 14, but is expected to preserve the integrity of the reading-frame (PMID: 12325021). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000673212 | SCV004216355 | pathogenic | Wilson disease | 2023-08-19 | criteria provided, single submitter | clinical testing |