ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2074+5G>A (rs587779880)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115287 SCV000149196 uncertain significance not provided 2014-02-26 criteria provided, single submitter clinical testing Single pathogenic variants in BLM have only recently been described in association with cancer predisposition and the risks are not well understood. This variant is denoted BLM IVS8+5G>A or c.2074+5G>A and consists of a G>A nucleotide substitution at the +5 position of intron 8 of the BLM gene. Multiple in silico models predict this variant to destroy the nearby natural donor site, and to possibly cause abnormal gene splicing. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BLM c.2074+5G>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant occurs at a position that is highly conserved across species. Based on the currently available information, we consider BLM c.2074+5G>A to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and with single variants the BLM gene in general, remain unclear.
Invitae RCV000812341 SCV000952652 uncertain significance Bloom syndrome 2018-12-14 criteria provided, single submitter clinical testing This sequence change falls in intron 8 of the BLM gene. It does not directly change the encoded amino acid sequence of the BLM protein, but it affects a nucleotide within the consensus splice site of the intron. 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. ClinVar contains an entry for this variant (Variation ID: 127481). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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