Total submissions: 3
| 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 | 2018-06-08 | 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. This variant is present in population databases (rs748240187, ExAC 0.002%). This variant has been observed on the opposite chromosome (in trans) from other pathogenic variants in individuals affected with Bloom syndrome (PMID: 17407155). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 188870). Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). For these reasons, this variant has been classified as Pathogenic. |
| Integrated Genetics/Laboratory Corporation of America | RCV000169224 | SCV000916686 | likely pathogenic | Bloom syndrome | 2018-08-17 | 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 (e.g. p.Trp428X, p.Asn515fsX16, p.Gln548X). The variant allele was found at a frequency of 7.2e-06 in 276670 control chromosomes (gnomAD). c.991_995delAAAGA has been reported in the literature in individuals affected with Bloom Syndrome (German 2007). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |