Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001027062 | SCV001189562 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-17 | criteria provided, single submitter | clinical testing | The c.801+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 8 of the POLE gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function via haploinsufficiency in POLE has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV001759922 | SCV001990433 | uncertain significance | not provided | 2019-07-17 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Canonical splice site variant predicted to result in an in-frame deletion of exon 8; Has not been previously published as pathogenic or benign to our knowledge |