Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000527173 | SCV000623345 | uncertain significance | Bloom syndrome | 2024-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 216 of the BLM protein (p.Glu216Lys). This variant is present in population databases (rs779934502, gnomAD 0.006%). 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: 454160). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV001025303 | SCV001187467 | likely benign | Hereditary cancer-predisposing syndrome | 2018-06-06 | 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 | RCV005000112 | SCV005624286 | uncertain significance | not provided | 2023-11-17 | criteria provided, single submitter | clinical testing | The BLM c.646G>A (p.Glu216Lys) variant has not been reported in individuals with BLM-related conditions in the published literature. The frequency of this variant in the general population, 0.000008 (2/250998 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using a bioinformatics tool for the prediction of the effect of amino acid changes on protein structure and function yielded a prediction that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |