ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.83C>G (p.Ser28Ter)

dbSNP: rs2151145090
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV001782196 SCV002018462 pathogenic Bloom syndrome 2021-05-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001782196 SCV002243052 pathogenic Bloom syndrome 2021-12-15 criteria provided, single submitter clinical testing 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). This sequence change creates a premature translational stop signal (p.Ser28*) 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).
Ambry Genetics RCV002440874 SCV002677742 likely pathogenic Hereditary cancer-predisposing syndrome 2022-10-12 criteria provided, single submitter clinical testing The p.S28* variant (also known as c.83C>G), located in coding exon 1 of the BLM gene, results from a C to G substitution at nucleotide position 83. This changes the amino acid from a serine to a stop codon within coding exon 1. The predicted stop codon occurs in the 5’ end of theBLM gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This alteration was detected in a cohort of 93,419 individuals undergoing a 96-gene expanded carrier screen (Kaseniit KE et al. Genet Med, 2020 10;22:1694-1702). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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