Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000115322 | SCV000149231 | uncertain significance | not provided | 2014-02-18 | 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.696C>A at the cDNA level, p.Ser232Arg (S232R) at the protein level, and results in the change of a Serine to an Arginine (AGC>AGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BLM Ser232Arg was not observed at significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a semi-conservative substitution in which a neutral polar amino acid is replaced with a positive polar one, altering a position that is only moderately conserved throughout evolution and is not located in a known functional domain (UniProt). In silico analyses predict this variant to have a benign effect on protein structure and function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and with single variants the BLM gene in general, remain unclear. |
Illumina Laboratory Services, |
RCV000326657 | SCV000394411 | uncertain significance | Bloom syndrome | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Invitae | RCV000326657 | SCV000623347 | likely benign | Bloom syndrome | 2023-12-27 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001025851 | SCV001188122 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-01 | criteria provided, single submitter | clinical testing | The p.S232R variant (also known as c.696C>A), located in coding exon 2 of the BLM gene, results from a C to A substitution at nucleotide position 696. The serine at codon 232 is replaced by arginine, an amino acid with dissimilar properties. This alteration was identified in an individual diagnosed with pancreatic cancer at 55. A CHEK2 mutation (c.1283C>T) was also identified (Cox DM et al. Mol Genet Genomic Med, 2018 11;6:1236-1242). This amino acid position is not well 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. |
Sema4, |
RCV001025851 | SCV002533151 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-19 | criteria provided, single submitter | curation |