ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2075-1G>A

gnomAD frequency: 0.00001  dbSNP: rs1231598990
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001014335 SCV001175031 likely pathogenic Hereditary cancer-predisposing syndrome 2021-02-17 criteria provided, single submitter clinical testing The c.2075-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 8 of the BLM gene. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001068255 SCV001233354 likely pathogenic Bloom syndrome 2024-05-13 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 8 of the BLM gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 820660). Studies have shown that disruption of this splice site results in skipping of exon 6 and activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001068255 SCV005640445 likely pathogenic Bloom syndrome 2024-01-03 criteria provided, single submitter clinical testing

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