Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001047756 | SCV001211736 | uncertain significance | Bloom syndrome | 2023-03-28 | 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. Variants that disrupt 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. ClinVar contains an entry for this variant (Variation ID: 844811). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 10 of the BLM gene. It does not directly change the encoded amino acid sequence of the BLM protein. It affects a nucleotide within the consensus splice site. |
| Ambry Genetics | RCV002445250 | SCV002734891 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-30 | criteria provided, single submitter | clinical testing | The c.2307+5G>C intronic variant results from a G to C substitution 5 nucleotides after coding exon 9 in the BLM 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 weaken the efficiency of 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. |