ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2480T>A (p.Met827Lys)

dbSNP: rs748250819
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000628648 SCV000749552 uncertain significance Bloom syndrome 2024-11-24 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 827 of the BLM protein (p.Met827Lys). This variant is present in population databases (rs748250819, 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: 524784). 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 expected to disrupt BLM protein function with a positive predictive value of 80%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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.
Fulgent Genetics, Fulgent Genetics RCV000628648 SCV000896484 uncertain significance Bloom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001015648 SCV001176505 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-10 criteria provided, single submitter clinical testing The p.M827K variant (also known as c.2480T>A), located in coding exon 11 of the BLM gene, results from a T to A substitution at nucleotide position 2480. The methionine at codon 827 is replaced by lysine, 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.