Submissions for variant NM_000251.3(MSH2):c.367-2_645+742del

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356643	SCV001551867	pathogenic	Lynch syndrome		no assertion criteria provided	clinical testing	The c.367-?_1386+?del deletion variant (chr2, g.47637291-?_47672775+?del (Genome assembly: GRCh37)) is predicted to cause an in-frame deletion of exons 3 through 8, although the precise breakpoints of this deletion were not determined, nor was the resulting effect on the mRNA or protein product. This variant was identified in 4 of 984 proband chromosomes (frequency: 0.004) from individuals with colon cancer (Baudhuin 2005, van der Klift 2005, Wagner 2003), and was reported in HGMD, the InSiGHT Colon Cancer database, and the “Mismatch Repair Genes Variant Database”. This alteration is predicted to result in a truncated or absent protein and loss of function, and is the type of variant expected to cause the disorder. In addition, Boyer (1995) described a colorectal tumour cell line which had a deletion of exons 3 through 8 in the MSH2 gene, and had no detectable wild-type copy of the MSH2 gene. This cell line displayed an elevated mutation rate at microsatellite sequences, and extracts of the cell line were defective in repairing substrates containing mismatches or unpaired nucleotides. In summary, based on the above information, this variant is classified as pathogenic.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357168	SCV001552542	pathogenic	Endometrial carcinoma		no assertion criteria provided	clinical testing	The c.367-?_1386+?del deletion variant (chr2, g.47637291-?_47672775+?del (Genome assembly: GRCh37)) is predicted to cause an in-frame deletion of exons 3 through 8, although the precise breakpoints of this deletion were not determined, nor was the resulting effect on the mRNA or protein product. This variant was identified in 4 of 984 proband chromosomes (frequency: 0.004) from individuals with colon cancer (Baudhuin 2005, van der Klift 2005, Wagner 2003), and was reported in HGMD, the InSiGHT Colon Cancer database, and the “Mismatch Repair Genes Variant Database”. This alteration is predicted to result in a truncated or absent protein and loss of function, and is the type of variant expected to cause the disorder. In addition, Boyer (1995) described a colorectal tumour cell line which had a deletion of exons 3 through 8 in the MSH2 gene, and had no detectable wild-type copy of the MSH2 gene. This cell line displayed an elevated mutation rate at microsatellite sequences, and extracts of the cell line were defective in repairing substrates containing mismatches or unpaired nucleotides. In summary, based on the above information, this variant is classified as pathogenic.