Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001247415 | SCV001420836 | pathogenic | Bloom syndrome | 2022-07-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 42088). This variant is also known as c.3727_3728dupA. This premature translational stop signal has been observed in individual(s) with Bloom syndrome (PMID: 17407155). This variant is present in population databases (rs367543021, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Thr1243Asnfs*14) 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). |
Ambry Genetics | RCV003162294 | SCV003855068 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-01-11 | criteria provided, single submitter | clinical testing | The c.3727dupA pathogenic mutation, located in coding exon 18 of the BLM gene, results from a duplication of A at nucleotide position 3727, causing a translational frameshift with a predicted alternate stop codon (p.T1243Nfs*14). This variant has been identified in the homozygous state in an individual diagnosed with Bloom syndrome (German J et al. Hum Mutat, 2007 Aug;28:743-53). 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. |
Gene |
RCV003441727 | SCV004169456 | pathogenic | not provided | 2023-05-10 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17407155) |
Natera, |
RCV001247415 | SCV002090598 | pathogenic | Bloom syndrome | 2017-03-16 | no assertion criteria provided | clinical testing |