Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000528231 | SCV000623222 | pathogenic | Bloom syndrome | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu377Serfs*6) 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 not present in population databases (gnomAD no frequency). 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: 454063). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002323901 | SCV002608434 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-28 | criteria provided, single submitter | clinical testing | The c.1129delG pathogenic mutation, located in coding exon 5 of the BLM gene, results from a deletion of one nucleotide at nucleotide position 1129, causing a translational frameshift with a predicted alternate stop codon (p.E377Sfs*6). This variant was identified in 1/317 men in a metastatic prostate cancer cohort undergoing hereditary cancer genetic testing (Boyle JL et al. JCO Precis Oncol, 2020 Mar;4:). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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. |