ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.403G>T (p.Ala135Ser) (rs373832397)

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
GeneDx RCV000115316 SCV000149225 uncertain significance not provided 2013-10-24 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.403G>T at the cDNA level, p.Ala135Ser (A135S) at the protein level, and results in the change of an Alanine to a Serine (GCT>TCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BLM Ala135Ser was not observed at significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a non-conservative substitution of a neutral non-polar amino acid for a positive polar one, altering a position that is highly variable throughout evolution and is not located in a known functional domain. 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. Based on the currently available information, cancer risks associated with this variant, and with single varaints the BLM gene in general, remain unclear.
Invitae RCV000465705 SCV000543342 uncertain significance Bloom syndrome 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 135 of the BLM protein (p.Ala135Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs373832397, ExAC 0.001%). This variant has not been reported in the literature in individuals with BLM-related disease. ClinVar contains an entry for this variant (Variation ID: 127508). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000566329 SCV000672961 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-07 criteria provided, single submitter clinical testing Insufficient evidence

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.