Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001015905 | SCV001176794 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-01 | criteria provided, single submitter | clinical testing | The p.Q851E variant (also known as c.2551C>G), located in coding exon 11 of the BLM gene, results from a C to G substitution at nucleotide position 2551. The glutamine at codon 851 is replaced by glutamic acid, 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 |
RCV001044147 | SCV001207928 | uncertain significance | Bloom syndrome | 2024-09-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 851 of the BLM protein (p.Gln851Glu). This variant is present in population databases (rs767638712, gnomAD 0.003%). 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: 821463). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003479264 | SCV004222889 | uncertain significance | not specified | 2023-11-20 | criteria provided, single submitter | clinical testing | Variant summary: BLM c.2551C>G (p.Gln851Glu) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 250962 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2551C>G in individuals affected with Bloom Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Gene |
RCV004761872 | SCV005370018 | uncertain significance | not provided | 2023-05-30 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Natera, |
RCV001044147 | SCV002088082 | uncertain significance | Bloom syndrome | 2018-11-13 | no assertion criteria provided | clinical testing |