Submissions for variant NM_000251.2(MSH2):c.-79G>A

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002877052	SCV003237663	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2022-09-25	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 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 variant occurs in a non-coding region of the MSH2 gene. It does not change the encoded amino acid sequence of the MSH2 protein.
Color Diagnostics, LLC DBA Color Health	RCV003585309	SCV004359286	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-02	criteria provided, single submitter	clinical testing	This variant causes an G to A nucleotide substitution at the -79 position in the 5' untranslated region in the MSH2 gene. This variant is located distal to the Kozak consensus sequence (PMID: 3313277) and the variant nucleotide is observed in multiple reference species at this position (PMID: 12519945), which suggest that this change may be functionally tolerated. 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.
All of Us Research Program, National Institutes of Health	RCV004007652	SCV004825295	uncertain significance	Lynch syndrome	2023-08-15	criteria provided, single submitter	clinical testing	This variant causes an G to A nucleotide substitution at the -79 position in the 5' untranslated region in the MSH2 gene. This variant is located distal to the Kozak consensus sequence (PMID: 3313277) and the variant nucleotide is observed in multiple reference species at this position (PMID: 12519945), which suggest that this change may be functionally tolerated. 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.