Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001355108 | SCV001549894 | pathogenic | Carcinoma of colon | no assertion criteria provided | clinical testing | The MSH2 c.212-?_1076+?del variant (chr:2 g.47635540_47643568del GRCh37) results in a deletion of exons 2 to 6, although the precise breakpoints of this deletion were not determined, nor were the effects of this variant on the resulting mRNA or protein product determined. The MSH2 p.Gly71Aspfsx2 variant was identified in the literature in 2 of 168 chromosomes (frequency: 0.012) from Chinese, Australian and Scottish individuals or families with CRC or HNPCC (Zhu_2005, Kohonen-Corish_1996, Davoodi_Semiromi_2000). The variant was identified by RNA analysis. The variant was also identified in ClinVar (classified pathogenic, reviewed by an expert panel (2013); submitters InSIGHT and Invitae), Zhejiang Colon Cancer Database (1x), Mismatch Repair Genes Variant Database (5x), and Insight Hereditary Tumors Database (1x); and was not identified in dbSNP, Clinvitae, COGR, Cosmic, UMD-LSDB, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.212-?_1076+?del variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 71 and leads to a premature stop codon 2 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the MSH2 gene are an established mechanism of disease in Lynch syndrome and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. |