Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001059018 | SCV001223621 | uncertain significance | Bloom syndrome | 2022-02-02 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 877 of the BLM protein (p.Asp877Gly). This variant is present in population databases (no rsID available, 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: 813653). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV002427455 | SCV002744726 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-18 | criteria provided, single submitter | clinical testing | The p.D877G variant (also known as c.2630A>G), located in coding exon 12 of the BLM gene, results from an A to G substitution at nucleotide position 2630. The aspartic acid at codon 877 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly 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. |
Department of Pediatrics, |
RCV001252873 | SCV001164016 | uncertain significance | Microcephaly | no assertion criteria provided | research | ||
Natera, |
RCV001059018 | SCV001454861 | uncertain significance | Bloom syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |