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: 7
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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.
Invitae RCV000550035 SCV000623281 benign Bloom syndrome 2024-01-27 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: 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 2022-05-02 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/). It has been reported in an individual with colorectal cancer (PMID: 28944238) and in a non-cancer control individual (PMID: 29641532). In silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Bloom syndrome. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000766552 SCV004222457 uncertain significance not provided 2022-12-13 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.00014 (18/129020 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with colorectal cancer (PMID: 28944238 (2017)), but also in a healthy cancer-free individual (PMID: 29641532 (2018)). 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.
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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