Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000562947 | SCV000672975 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-28 | 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. |
| Labcorp Genetics |
RCV000628644 | SCV000749548 | uncertain significance | Bloom syndrome | 2024-09-25 | 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). 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 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 (internal data). 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, |
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 | 2024-08-12 | criteria provided, single submitter | clinical testing | The BLM c.2674A>G (p.Ile892Val) variant has not been reported in individuals with BLM-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/251326 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, |
RCV000628644 | SCV002088102 | uncertain significance | Bloom syndrome | 2018-11-29 | no assertion criteria provided | clinical testing |