Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000204446 | SCV000259260 | uncertain significance | Lynch syndrome | 2015-07-02 | criteria provided, single submitter | clinical testing | This sequence change affects codon 179 of the PMS2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PMS2 protein. It also falls at the last nucleotide of exon 5 of the PMS2 mRNA. This variant has not been published in the literature and is not present in population databases. Algorithms developed to predict the effect of silent changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a novel silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002345727 | SCV002646970 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-09-29 | criteria provided, single submitter | clinical testing | The c.537G>A variant (also known as p.K179K), located in coding exon 5 of the PMS2 gene, results from a G to A substitution at nucleotide position 537. This nucleotide substitution does not change the lysine at codon 179. However, this change occurs in the last base pair of coding exon 5, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is well 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |