Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Myriad Genetics, |
RCV004789542 | SCV005402861 | benign | Hereditary diffuse gastric adenocarcinoma | 2024-09-18 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
Department of Pathology and Laboratory Medicine, |
RCV001356039 | SCV001551093 | likely benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The CDH1 p.Asp479= variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, Cosmic, MutDB, LOVD 3.0, Zhejiang Colon Cancer Database, 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 p.Asp479= 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. The variant was also identified by our laboratory in 1 individual with breast cancer, co-occurring with a pathogenic BRCA1 variant (c.3286C>T, p.Gln1096X), increasing the likelihood the p.Asp479= variant does not have clinical significance. 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. |