Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000628617 | SCV000749519 | uncertain significance | Bloom syndrome | 2022-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 70 of the BLM protein (p.Asp70Asn). This variant is present in population databases (rs769957028, gnomAD 0.002%). 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: 524758). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 | RCV001014393 | SCV001175093 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-28 | criteria provided, single submitter | clinical testing | The p.D70N variant (also known as c.208G>A), located in coding exon 2 of the BLM gene, results from a G to A substitution at nucleotide position 208. The aspartic acid at codon 70 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is poorly 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, |
RCV001014393 | SCV002533726 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-19 | criteria provided, single submitter | curation | |
Natera, |
RCV000628617 | SCV001456632 | uncertain significance | Bloom syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |