Submissions for variant NM_000057.4(BLM):c.864del (p.Pro287_Cys288insTer)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002877204	SCV003238310	pathogenic	Bloom syndrome	2022-10-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Cys288*) 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). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is not present in population databases (gnomAD no frequency).
Neuberg Centre For Genomic Medicine, NCGM	RCV002877204	SCV005374753	uncertain significance	Bloom syndrome		criteria provided, single submitter	clinical testing	The observed frameshift c.864del (p.Cys288Ter) variant in BLM gene has been submitted to the ClinVar database as Pathogenic. The p.Cys288Ter variant is absent in gnomAD Exomes. This sequence change creates a premature translational stop signal (p.Cys288Ter) in the BLM gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in BLM gene have been previously reported to be disease causing (German et al., 2007). Additional functional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as Likely Pathogenic.