Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000691177 | SCV000818923 | uncertain significance | Bloom syndrome | 2024-12-10 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 295 of the BLM protein (p.Asp295Tyr). This variant is present in population databases (rs146096923, gnomAD 0.02%). 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: 570334). 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 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 | RCV001018386 | SCV001179618 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-05 | criteria provided, single submitter | clinical testing | The p.D295Y variant (also known as c.883G>T), located in coding exon 3 of the BLM gene, results from a G to T substitution at nucleotide position 883. The aspartic acid at codon 295 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| St. |
RCV000691177 | SCV005402385 | uncertain significance | Bloom syndrome | 2023-12-19 | criteria provided, single submitter | clinical testing | The BLM c.883G>T (p.Asp295Tyr) missense change has a maximum subpopulation frequency of 0.02% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Bloom syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
| Natera, |
RCV000691177 | SCV002089984 | uncertain significance | Bloom syndrome | 2018-10-06 | no assertion criteria provided | clinical testing |