Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000468134 | SCV000543394 | uncertain significance | Bloom syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 507 of the BLM protein (p.Glu507Lys). This variant is present in population databases (rs192491153, gnomAD 0.006%). This missense change has been observed in individual(s) with breast cancer (PMID: 31780696). ClinVar contains an entry for this variant (Variation ID: 405326). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BLM protein function with a negative predictive value of 80%. 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 | RCV000574215 | SCV000672954 | likely benign | Hereditary cancer-predisposing syndrome | 2018-03-26 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Genetic Services Laboratory, |
RCV001821235 | SCV002071897 | uncertain significance | not specified | 2021-10-01 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the BLM gene demonstrated a sequence change, c.1519G>A, in exon 7 that results in an amino acid change, p.Glu507Lys. This sequence change has been described in the gnomAD database with a frequency of 0.0087% in the Latino/Admixed American subpopulation (dbSNP rs192491153). The p.Glu507Lys change affects a moderately conserved amino acid residue located in a domain of the BLM protein that is not known to be functional. The p.Glu507Lys substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change has previously been described in an individual with breast cancer (PMID: 31780696). Due to insufficient evidence and the lack of functional studies, the clinical significance of the p.Glu507Lys change remains unknown at this time. |
| Sema4, |
RCV000574215 | SCV002531349 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-25 | criteria provided, single submitter | curation | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477944 | SCV004222433 | uncertain significance | not provided | 2023-02-10 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.000087 (3/34572 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with breast cancer (PMID: 31780696 (2019)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |