ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1386+4T>C

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003362414 SCV004081972 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-24 criteria provided, single submitter clinical testing The c.1386+4T>C intronic variant results from a T to C substitution 4 nucleotides after coding exon 8 in the MSH2 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV003759832 SCV004463656 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-09-05 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. This sequence change falls in intron 8 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. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. 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.
All of Us Research Program, National Institutes of Health RCV004011284 SCV004829515 uncertain significance Lynch syndrome 2023-05-16 criteria provided, single submitter clinical testing This variant causes a T to C nucleotide substitution at the +4 position of intron 8 of the MSH2 gene. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional 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.

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