Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000115293 | SCV000149202 | uncertain significance | not provided | 2014-02-17 | criteria provided, single submitter | clinical testing | Single pathogenic variants in BLM have only recently been described in association with cancer predisposition and the risks are not well understood. This variant is denoted BLM c.2452_2454delCGCinsGGG at the cDNA level and consists of a substitution of three adjacent nucleotides (CGC) with three others (GGG). At the protein level, this variant is denoted p.Arg818Gly (R818G) and results in a change from an Arginine to a Glycine (CGC>GGG). The c.2452C>G and c.2454C>G adjacent variants were determined to be on the same chromosome (in cis) by Next Generation Sequencing. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BLM c.2452_2454delCGCinsGGG was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This variant is a non-conservative amino acid substitution, altering a position that is fully conserved throughout evolution and located within the Helicase ATPase-binding domain. Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. We consider BLM c.2452_2454delCGCinsGGG to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and with single variants in the BLM gene in general, remain unclear. |
| Ambry Genetics | RCV001015588 | SCV001176437 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-29 | criteria provided, single submitter | clinical testing | The c.2452_2454delCGCinsGGG variant (also known as p.R818G), located in coding exon 11 of the BLM gene, results from an in-frame deletion of CGC and insertion of GGG at nucleotide positions 2452 to 2454. This results in the substitution of the arginine residue for a glycine residue at codon 818, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |