ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2674A>G (p.Ile892Val)

gnomAD frequency: 0.00001  dbSNP: rs764587569
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562947 SCV000672975 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-21 criteria provided, single submitter clinical testing The p.I892V variant (also known as c.2674A>G), located in coding exon 13 of the BLM gene, results from an A to G substitution at nucleotide position 2674. The isoleucine at codon 892 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000628644 SCV000749548 uncertain significance Bloom syndrome 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 892 of the BLM protein (p.Ile892Val). This variant is present in population databases (rs764587569, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 485341). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BLM protein function with a positive predictive value of 80%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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.
Fulgent Genetics, Fulgent Genetics RCV000628644 SCV002787385 uncertain significance Bloom syndrome 2021-08-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478277 SCV004222461 uncertain significance not provided 2023-06-27 criteria provided, single submitter clinical testing This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0000088 (1/113684 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 damaging. Additional analysis using software algorithms for the prediction of the effect of nucleotide changes on BLM mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites . Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000628644 SCV002088102 uncertain significance Bloom syndrome 2018-11-29 no assertion criteria provided clinical testing

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