The c.2450C>T (p.Ala817Val) variant results in a missense change in the last exon of CDH1. This variant is present at a frequency 3.3x10-5 (5 of 152,172 alleles) in the gnomAD population database v3.1.2. This variant has been observed in 104 individuals without DGC, LBC or SRC tumours and whose families do not suggest HDGC (BS2; internal laboratory contributors). In vitro studies of the A817V variant suggest reduced binding of B-catenin and reduced cell aggregation in a HEK293T cell model (PMID: 33929593). However, evaluation of the use of functional data by the VCEP indicates that functional data currently available for missense variants cannot yet predict the pathogenicity of CDH1 variants, and it is therefore not considered in the classification for any CDH1 missense variant (Lee et al, 2018; PMID: 30311375). As such, published information from in vitro or in vivo assays assessing impact on function for this missense variant has not been considered for variant curation. In summary, this variant is classified as likely benign based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel: BS2.