ClinVar

Description

The CDH1 p.Asp881= variant was not identified in the literature nor was it identified in the Zhejiang University database. The variant was identified in dbSNP (ID: rs114708971) as "With Likely benign allele" , ClinVar (classified as benign by GeneDx; as likely benign by Ambry Genetics, Invitae and Color Genomics), and in Cosmic (1x in bone tissue) databases. The variant was identified in control databases in 19 of 277124 chromosomes at a frequency of 0.0001 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 6 of 24030 chromosomes (freq: 0.0003), Other in 1 of 6466 chromosomes (freq: 0.0002), Latino in 3 of 34418 chromosomes (freq: 0.0001), European in 8 of 126640 chromosomes (freq: 0.0001), and South Asian in 1 of 30782 chromosomes (freq: 0.00003), while the variant was not observed in the Ashkenazi Jewish, East Asian, and Finnish populations. The p.Asp881= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.