Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003651887 | SCV000552734 | uncertain significance | Familial adenomatous polyposis 1 | 2023-11-07 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 4 of the APC gene. It does not directly change the encoded amino acid sequence of the APC protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with APC-related conditions (PMID: 25676610). ClinVar contains an entry for this variant (Variation ID: 411534). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 5 and introduces a premature termination codon (PMID: 25676610). The resulting mRNA is expected to undergo nonsense-mediated decay. 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. |
Ambry Genetics | RCV003298503 | SCV004001059 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | clinical testing | The c.423-4_423-2delATA intronic variant, located in intron 3 of the APC gene, results from a deletion of 3 nucleotides within intron 3 of the APC gene. This alteration has been reported in the literature in a family affected with Cenani-Lenz syndrome (Patel N et al. J Med Genet, 2015 May;52:317-21; Maddirevula S et al. Genet Med, 2018 Dec;20:1609-1616). Although these nucleotides are located near a canonical splice site, the canonical splice acceptor "ag" sequence is preserved. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data; Patel N et al. J Med Genet, 2015 May;52:317-21; Maddirevula S et al. Genome Biol, 2020 Jun;21:145). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
OMIM | RCV000185617 | SCV000238529 | uncertain significance | not provided | 2015-05-01 | no assertion criteria provided | literature only |