ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1076+4T>C

gnomAD frequency: 0.00001  dbSNP: rs764606343
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217421 SCV000278674 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-12 criteria provided, single submitter clinical testing The c.1076+4T>C intronic variant results from a T to C substitution 4 nucleotides after coding exon 6 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.
Color Diagnostics, LLC DBA Color Health RCV000217421 SCV000908292 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-29 criteria provided, single submitter clinical testing This variant causes a T>C nucleotide substitution at the +4 position of the intron 6 of the MSH2 gene. To our knowledge, RNA studies have not been performed for this variant. 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 been identified in 3/251386 chromosomes 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.
Invitae RCV001854722 SCV002122524 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-09-07 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. 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. This variant has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 234155). This variant is present in population databases (rs764606343, ExAC 0.02%). This sequence change falls in intron 6 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.
All of Us Research Program, National Institutes of Health RCV003998604 SCV004837589 uncertain significance Lynch syndrome 2023-10-06 criteria provided, single submitter clinical testing This variant causes a T>C nucleotide substitution at the +4 position of the intron 6 of the MSH2 gene. To our knowledge, RNA studies have not been performed for this variant. 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 been identified in 3/251386 chromosomes 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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