ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2561G>A (p.Ser854Asn)

gnomAD frequency: 0.00001  dbSNP: rs758692622
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000628681 SCV000749587 uncertain significance Bloom syndrome 2024-11-19 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 854 of the BLM protein (p.Ser854Asn). This variant is present in population databases (rs758692622, gnomAD 0.009%). This missense change has been observed in individual(s) with breast cancer (PMID: 31780696, 35264596). ClinVar contains an entry for this variant (Variation ID: 524813). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BLM protein function with a negative predictive value of 80%. 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.
Mendelics RCV000628681 SCV000838974 uncertain significance Bloom syndrome 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001015940 SCV001176835 likely benign Hereditary cancer-predisposing syndrome 2023-10-24 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478339 SCV004222456 uncertain significance not provided 2023-10-23 criteria provided, single submitter clinical testing The BLM c.2561G>A (p.Ser854Asn) variant has been reported in the published literature in individuals with breast cancer (PMID: 31780696 (2019), 35264596 (2022)). The frequency of this variant in the general population, 0.000087 (3/34498 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.
Natera, Inc. RCV000628681 SCV002088087 uncertain significance Bloom syndrome 2018-12-26 no assertion criteria provided clinical testing

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