Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000582622 | SCV000686827 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-02-25 | criteria provided, single submitter | clinical testing | This variant causes an A>T nucleotide substitution at the -2 position of intron 11 of the APC gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of APC function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. |
| Myriad Genetics, |
RCV003336059 | SCV004043063 | likely pathogenic | Familial adenomatous polyposis 1 | 2023-05-01 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
| Department of Pathology and Laboratory Medicine, |
RCV001356338 | SCV001551475 | pathogenic | not provided | no assertion criteria provided | clinical testing | The APC c.1409-2A>T variant was not identified in the literature nor was it identified in dbSNP, ClinVar, GeneInsight-COGR, Cosmic, MutDB, UMD-LSDB, Insight Colon Cancer Gene Variant Database, 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 c.1409-2A>T variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition, 5 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. An alternate variant c.1409-2A>G was identified in 1 proband with attenuated polyposis diagnosed at age 29 and mRNA transcript analysis using peripheral blood confirmed exon 11 skipping (Aretz_2004_15459959). In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. |