Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000701067 | SCV000829849 | uncertain significance | Bloom syndrome | 2022-10-04 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 578145). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1292 of the BLM protein (p.Ala1292Asp). |
Ambry Genetics | RCV002352193 | SCV002620534 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-10 | criteria provided, single submitter | clinical testing | The p.A1292D variant (also known as c.3875C>A) is located in coding exon 20 of the BLM gene. The alanine at codon 1292 is replaced by aspartic acid, an amino acid with dissimilar properties. This change occurs in the first base pair of coding exon 20. This amino acid position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV003322813 | SCV004028053 | uncertain significance | not provided | 2023-02-16 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV000701067 | SCV002090621 | uncertain significance | Bloom syndrome | 2021-03-24 | no assertion criteria provided | clinical testing |