Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001035013 | SCV001198318 | likely pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-08-12 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 6 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has not been reported in the literature in individuals with MSH2-related conditions. This variant is not present in population databases (ExAC no frequency). |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800940 | SCV002046530 | likely pathogenic | not provided | 2020-12-28 | criteria provided, single submitter | clinical testing | This variant is located in a canonical splice-donor site and is predicted to interfere with normal MSH2 mRNA splicing. To the best of our knowledge, the variant has not been reported in the published literature. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant may affect proper MSH2 mRNA splicing. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Based on the available information, we predict that the variant is likely pathogenic. |
Myriad Genetics, |
RCV003455146 | SCV004186651 | likely pathogenic | Lynch syndrome 1 | 2023-07-31 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |