Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000793913 | SCV000933292 | uncertain significance | Bloom syndrome | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 274 of the BLM protein (p.Asn274Asp). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 640809). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
St. |
RCV000793913 | SCV002584629 | uncertain significance | Bloom syndrome | 2022-09-09 | criteria provided, single submitter | clinical testing | The BLM c.820A>G (p.Asn274Asp) missense change has a maximum subpopulation frequency of 0.011% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Bloom syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Ambry Genetics | RCV002424800 | SCV002679723 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-24 | criteria provided, single submitter | clinical testing | The p.N274D variant (also known as c.820A>G), located in coding exon 3 of the BLM gene, results from an A to G substitution at nucleotide position 820. The asparagine at codon 274 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV003226978 | SCV003923797 | uncertain significance | not provided | 2022-11-07 | 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, |
RCV000793913 | SCV001456651 | uncertain significance | Bloom syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |