ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2638G>C (p.Glu880Gln)

gnomAD frequency: 0.00011  dbSNP: rs201770808
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766552 SCV000149205 uncertain significance not provided 2014-01-10 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 c.2638G>C at the cDNA level, p.Glu880Gln (E880Q) at the protein level, and results in the change of a Glutamic Acid to a Glutamine (GAA>CAA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BLM Glu880Gln was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a semi-conservative substitution in which a negative polar amino acid is replaced with a neutral polar one, altering a position that is well conserved throughout evolution and is located within the Helicase C-terminal domain. In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000550035 SCV000623281 benign Bloom syndrome 2025-02-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000567138 SCV000672933 likely benign Hereditary cancer-predisposing syndrome 2022-01-31 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000550035 SCV002526039 uncertain significance Bloom syndrome 2025-02-05 criteria provided, single submitter clinical testing The BLM c.2638G>C p.(Glu880Gln) missense change has a maximum subpopulation frequency of 0.014% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. This variant has been reported in an individual with colorectal cancer (PMID: 28944238) and in a non-cancer control (PMID: 29641532). To our knowledge, this variant has not been reported in individuals with Bloom syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000766552 SCV004222457 uncertain significance not provided 2023-12-18 criteria provided, single submitter clinical testing The BLM c.2638G>C (p.Glu880Gln) variant has been reported in the published literature in an individual with colorectal cancer (PMID: 28944238 (2017)) as well as in a reportedly healthy individual (PMID: 29641532 (2018)). The frequency of this variant in the general population, 0.00014 (18/129020 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Baylor Genetics RCV000550035 SCV005058121 uncertain significance Bloom syndrome 2024-03-26 criteria provided, single submitter clinical testing
ITMI RCV000120227 SCV000084374 not provided not specified 2013-09-19 no assertion provided reference population
Natera, Inc. RCV000550035 SCV001454862 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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