ClinVar

Description

The CDH1 c.832+1G>A variant was identified in 1 of 86 proband chromosomes (frequency: 0.01) from individuals or families with diffuse gastric cancer (Brooks-Wilson 2004). The variant was also identified in ClinVar (classified as likely pathogenic by Invitae) and Cosmic (2x in breast tissue). The variant was not identified in dbSNP, the Zhejiang University Database, or the following control databases: 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.832+1G>A variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition, 4 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing. It is predicted that the aberrant splicing would result in an in-frame deletion of exon 5 from the transcript, which is expected to be deleterious to the protein function (Brooks-Wilson 2004). In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.