Submissions for variant NM_000251.2(MSH2):c.-78T>A

gnomAD frequency: 0.00001  dbSNP: rs876658616

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000218583	SCV000274106	uncertain significance	Hereditary cancer-predisposing syndrome	2019-01-15	criteria provided, single submitter	clinical testing	The c.-78T>A variant is located in the 5' untranslated region (5’ UTR) of the MSH2 gene. This variant results from a T to A substitution 78 bases upstream from the first translated codon. This variant has been identified in individuals whose Lynch syndrome associated tumors were microsatellite stable (MSS) or demonstrated normal mismatch repair protein expression on immunohistochemistry (Ambry internal data). This nucleotide position is poorly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000218583	SCV002052434	uncertain significance	Hereditary cancer-predisposing syndrome	2023-01-18	criteria provided, single submitter	clinical testing	This variant causes a T to A nucleotide substitution in the 5' untranslated region of the MSH2 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in individuals whose Lynch syndrome-associated tumors were microsatellite stable or demonstrated normal mismatch repair protein expression on immunohistochemistry (ClinVar SCV000274106.5). 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.