Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000169224 | SCV000220489 | likely pathogenic | Bloom syndrome | 2014-07-08 | criteria provided, single submitter | literature only | |
| Invitae | RCV000169224 | SCV000833351 | pathogenic | Bloom syndrome | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys331Glyfs*4) 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 (rs748240187, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Bloom syndrome (PMID: 17407155). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 188870). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169224 | SCV000916686 | pathogenic | Bloom syndrome | 2022-04-01 | criteria provided, single submitter | clinical testing | Variant summary: BLM c.991_995delAAAGA (p.Lys331GlyfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251002 control chromosomes. c.991_995delAAAGA has been reported in the literature in at-least one individual affected with Bloom Syndrome (example, German_2007). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Ambry Genetics | RCV001019885 | SCV001181297 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-21 | criteria provided, single submitter | clinical testing | The c.991_995delAAAGA pathogenic mutation, located in coding exon 4 of the BLM gene, results from a deletion of 5 nucleotides at nucleotide positions 991 to 995, causing a translational frameshift with a predicted alternate stop codon (p.K331Gfs*4). Two individuals with Bloom syndrome were reported to be heterozygous for this alteration and another BLM gene mutation (German J et al. Hum. Mutat. 2007 Aug;28:743-53). 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. |