ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2555+1G>A

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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 RCV002433332 SCV002742973 likely pathogenic Hereditary cancer-predisposing syndrome 2021-03-08 criteria provided, single submitter clinical testing The c.2555+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 11 of the BLM gene. This variant is considered to be rare based on population 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 donor site and may result in the creation or strengthening of a novel splice donor 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 RCV003101966 SCV003522553 likely pathogenic Bloom syndrome 2022-07-16 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change affects a donor splice site in intron 12 of the BLM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. 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.
Baylor Genetics RCV003101966 SCV004210897 likely pathogenic Bloom syndrome 2023-04-18 criteria provided, single submitter clinical testing

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