Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000694716 | SCV000823173 | pathogenic | Bloom syndrome | 2024-02-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Met951Leufs*9) in the BLM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 573132). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000694716 | SCV002011811 | likely pathogenic | Bloom syndrome | 2019-07-05 | criteria provided, single submitter | clinical testing | This variant creates a premature translational stop signal described as p.Met951LeufsTer9 in the BLM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BLM have been previously described as pathogenic (PMID: 17407155). To the best of our knowledge, this variant has not been described in medical literature and it is not present on the gnomAD exomes database. Based on these findings and the limited literature regarding this substitution we consider it a “likely pathogenic variant”. |
| Ambry Genetics | RCV002440472 | SCV002752733 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-31 | criteria provided, single submitter | clinical testing | The c.2851_2857delATGGGGA pathogenic mutation, located in coding exon 14 of the BLM gene, results from a deletion of 7 nucleotides at nucleotide positions 2851 to 2857, causing a translational frameshift with a predicted alternate stop codon (p.M951Lfs*9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Baylor Genetics | RCV000694716 | SCV004210891 | pathogenic | Bloom syndrome | 2023-12-30 | criteria provided, single submitter | clinical testing |