Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001214637 | SCV001386326 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-04-18 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 13 of the MSH2 gene. It does not directly change the encoded amino acid sequence of the MSH2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related conditions. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002429913 | SCV002730814 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-06 | criteria provided, single submitter | clinical testing | The c.2211-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 14 in the MSH2 gene. This nucleotide position is not well conserved in available vertebrate species. This splice prediction software predicts a weakening in the native splice acceptor site efficiency. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |