ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1661+5G>C (rs267607972)

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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 RCV000490916 SCV000580545 likely pathogenic Hereditary cancer-predisposing syndrome 2013-12-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Other strong data supporting pathogenic classification
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000076218 SCV000592511 pathogenic Lynch syndrome 2016-08-17 criteria provided, single submitter clinical testing
Invitae RCV000812895 SCV000953225 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-22 criteria provided, single submitter clinical testing This sequence change falls in intron 10 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 present in population databases (rs267607972, ExAC 0.001%). This variant has been observed in individuals affected with Lynch syndrome-related cancer (PMID: 12362047, 25081409, 27601186). ClinVar contains an entry for this variant (Variation ID: 90721). 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 may disrupt the consensus splice site, 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.

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