Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000412101 | SCV000486627 | likely pathogenic | Bloom syndrome | 2016-07-06 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001017226 | SCV001178271 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-07-17 | criteria provided, single submitter | clinical testing | The c.1083_1084delTG variant, located in coding exon 4 of the BLM gene, results from a deletion of two nucleotides at nucleotide positions 1083 to 1084, causing a translational frameshift with a predicted alternate stop codon (p.C361*). This variant was identified in 1/857 unrelated cases of undefined familial colorectal cancer that were negative for a mutation in a known cancer susceptibility gene for colorectal cancer (CRC) (Dobbins SE et al. Fam. Cancer, 2016 10;15:593-9). This variant was also identified in 1/1006 familial early onset colorectal cancer patients as part of a case-control enrichment analysis that was performed using a publicly available independent cohort of 1006 patients of familial early-onset CRC (CanVar) and the Exome Aggregation Consortium (ExAC) database (Díaz-Gay M et al. Cancers (Basel), 2019 11;3:362). Of note, this alteration is also designated as c.1081_1082delTG in the published literature. 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. |
| Invitae | RCV000412101 | SCV001591498 | pathogenic | Bloom syndrome | 2023-09-03 | 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: 371130). This variant is also known as c.1081_1082delTG. This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 27356891). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Cys361*) 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). |