Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000816422 | SCV000956930 | likely pathogenic | Wilson disease | 2022-06-26 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 14 of the ATP7B gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 659418). This variant has not been reported in the literature in individuals affected with ATP7B-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| ARUP Laboratories, |
RCV000816422 | SCV004563302 | likely pathogenic | Wilson disease | 2023-09-21 | criteria provided, single submitter | clinical testing | The ATP7B c.3243+2T>C variant (rs1593671769), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 659418). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant disrupts the canonical splice donor site of intron 14, which is likely to negatively impact gene function. Based on available information, this variant is considered to be likely pathogenic. |
| All of Us Research Program, |
RCV000816422 | SCV004825110 | likely pathogenic | Wilson disease | 2024-07-29 | criteria provided, single submitter | clinical testing | This variant causes a T>C nucleotide substitution at the +2 position of intron 14 of the ATP7B gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with ATP7B-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. |
| Mayo Clinic Laboratories, |
RCV004792524 | SCV005414177 | likely pathogenic | not provided | 2023-12-11 | criteria provided, single submitter | clinical testing | PM2_moderate, PM3_supporting, PVS1_strong |