Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001371339 | SCV001567898 | uncertain significance | Bloom syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 1076 of the BLM protein (p.Asp1076Glu). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Sema4, |
RCV002259109 | SCV002530116 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-06 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002259109 | SCV003863725 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-10 | criteria provided, single submitter | clinical testing | The p.D1076E variant (also known as c.3228T>G), located in coding exon 16 of the BLM gene, results from a T to G substitution at nucleotide position 3228. The aspartic acid at codon 1076 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. 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. |