ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2875C>T (p.Arg959Ter)

dbSNP: rs762354041
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000469284 SCV000543314 pathogenic Bloom syndrome 2024-09-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg959*) 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 present in population databases (rs762354041, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 28724667). ClinVar contains an entry for this variant (Variation ID: 405266). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (internal data). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000469284 SCV000893391 pathogenic Bloom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002436391 SCV002751125 pathogenic Hereditary cancer-predisposing syndrome 2024-03-26 criteria provided, single submitter clinical testing The p.R959* variant (also known as c.2875C>T), located in coding exon 14 of the BLM gene, results from a C to T substitution at nucleotide position 2875. This changes the amino acid from an arginine to a stop codon within coding exon 14. This alteration was detected in a cohort of 8085 consecutive unselected Chinese breast cancer patients who underwent multi-gene panel testing. (Sun J et al. Clin. Cancer Res., 2017 Oct;23:6113-6119). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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.

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