Submissions for variant NM_000057.4(BLM):c.2991_2995del (p.Val998fs)

dbSNP: rs2151184718

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001893400	SCV002159030	pathogenic	Bloom syndrome	2020-11-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val998Glnfs*23) 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 not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BLM-related conditions. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV004041441	SCV005022671	pathogenic	Hereditary cancer-predisposing syndrome	2023-11-15	criteria provided, single submitter	clinical testing	The c.2991_2995delTGTGA pathogenic mutation, located in coding exon 14 of the BLM gene, results from a deletion of 5 nucleotides at nucleotide positions 2991 to 2995, causing a translational frameshift with a predicted alternate stop codon (p.V998Qfs*23). 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.