ClinVar

Description

The MSH6 c.3554_3556+2delCAGGT variant was not identified in the literature nor was it identified in dbSNP, Clinvitae database, COSMIC, Mismatch Repair Genes Variant Database, MMR Gene Unclassified Variants Database, InSiGHT Colon Cancer Gene Variant Database (LOVD), Zhejiang Colon Cancer Database (LOVD), ClinVar database, GeneInsight-COGR database, UMD, the 1000 Genomes Project, NHLBI GO Exome Sequencing Project, and the Exome Aggregation Consortium database (August 8, 2016). The c.3554_3556+2delCAGGT variant is located in the 5' splice donor region deleting the last three bases of the exon and first 2 bases of the intron. This position has been shown to be part of the splicing consensus sequence and invariant +1 and +2 positions, and variants involving this position sometimes affect splicing. In silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict the abolishment of the 5' splice site in this region, shifting it 5 base pairs upstream; however, this information is not predictive enough to assume pathogenicity. Protein-level nomenclature for this variant was predicted as p.Ser1185_Gly1186delinsCys. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.