Submissions for variant NM_000057.4(BLM):c.2187del (p.Leu730fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002510388	SCV002819645	likely pathogenic	Bloom syndrome	2022-12-19	criteria provided, single submitter	clinical testing	Variant summary: BLM c.2187delC (p.Leu730TrpfsX8) 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 251280 control chromosomes. To our knowledge, no occurrence of c.2187delC in individuals affected with Bloom Syndrome and no experimental evidence demonstrating its impact on protein function have 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.
Invitae	RCV002510388	SCV004655555	pathogenic	Bloom syndrome	2023-01-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu730Trpfs*8) 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. ClinVar contains an entry for this variant (Variation ID: 1878335). 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).