Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000555844 | SCV000625484 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-11-24 | criteria provided, single submitter | clinical testing | 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. Variants that disrupt 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. ClinVar contains an entry for this variant (Variation ID: 455626). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 5 of the MSH2 gene. It does not directly change the encoded amino acid sequence of the MSH2 protein. It affects a nucleotide within the consensus splice site. |
Ambry Genetics | RCV000564397 | SCV000669735 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-12-08 | criteria provided, single submitter | clinical testing | The c.942+5A>C intronic variant results from an A to C substitution 5 nucleotides after coding exon 5 in the MSH2 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV004003756 | SCV004832289 | uncertain significance | Lynch syndrome | 2023-08-23 | criteria provided, single submitter | clinical testing | This variant causes an A to C nucleotide substitution at the +5 position of intron 5 of the MSH2 gene. Splice site prediction tools suggest that this variant may (not) impact RNA splicing. To our knowledge, RNA studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |