Submissions for variant NC_000015.9:g.(?_91352357)_(91358509_?)del

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001379837	SCV001577711	likely pathogenic	Bloom syndrome	2022-09-25	criteria provided, single submitter	clinical testing	This variant is a gross deletion of the genomic region encompassing exon(s) 20-22 of the BLM gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. A similar copy number variant has been observed in individual(s) with Bloom syndrome (PMID: 17407155). This variant disrupts a region of the BLM protein in which other variant(s) (p.Ile1319Asnfs*87) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.