Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001041015 | SCV001204609 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-31 | criteria provided, single submitter | clinical testing | 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with RAD50-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 12 of the RAD50 gene. It does not directly change the encoded amino acid sequence of the RAD50 protein, but it affects a nucleotide within the consensus splice site of the intron. |
| Ambry Genetics | RCV001041015 | SCV002718937 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-18 | criteria provided, single submitter | clinical testing | The c.1969+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 12 in the RAD50 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |