Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220158 | SCV000277756 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-30 | criteria provided, single submitter | clinical testing | The p.Y2838* variant (also known as c.8514C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 8514. This changes the amino acid from a tyrosine to a stop codon within coding exon 15. This alteration occurs at the 3' terminus of the APC gene, is not expected to trigger nonsense mediated mRNA decay, and only impacts the last 6 amino acids of the protein. However, premature stop codons are typically deleterious in nature and structural analysis suggests this deletion removes a known motif (Thr2841-Ser2842-Val2843) needed for protein binding involved in regulation of protein function (Slep KC et al, PLoS ONE 2012; 7(11):e50097; Zhang Z et al, PLoS ONE 2011; 6(8):e23507). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV004563209 | SCV002268169 | uncertain significance | Familial adenomatous polyposis 1 | 2021-03-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr2838*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 6 amino acid(s) of the APC protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 233392). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |