Submissions for variant NM_002354.3(EPCAM):c.904-1_904del

dbSNP: rs2103770769

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetica Molecular, Fundacion para el Progreso de la Medicina	RCV002274255	SCV002549758	likely pathogenic	Lynch syndrome 1	2022-06-03	no assertion criteria provided	clinical testing	In the patient under study, a variant was found in exon 9 of the EPCAM gene, in a heterozygous state, consisting of a deletion of two nucleotides (c.904-1_904del), one of which is found in the intronic region adjacent to the exon 9, and the other at the first nucleotide of the same exon. This alteration would produce a stop codon in the first codon of exon 9 (p.(Ile302Ter)), stopping protein synthesis and leaving the protein without the last 13 amino acids. This alteration is unprecedented in mutational databases (ClinVar, LOVD-Variome, SITHER), population databases (GenomAD, ESP5400), as well as in reports or bibliography. There is a very close variant, c.904-2A>G (ClinVar: VCV000239144.3. dbSNPs: rs878854496), which, despite being of a different nature, causes a disruption in splicing with the production of a probable abnormal protein. It has been observed that most patients with deletions at the 3' end of the EPCAM gene report inactivation of MSH2. This patient has a defective MSH2 protein (iNMUNOHISTOCHEMISTRY) and positive CNVs analysis in the MSH2 gene