Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000414432 | SCV000491977 | uncertain significance | not specified | 2016-11-23 | criteria provided, single submitter | clinical testing | The N2159S variant in the LRBA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N2159S variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N2159S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret N2159S as a variant of uncertain significance |
Invitae | RCV000801747 | SCV000941541 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 2159 of the LRBA protein (p.Asn2159Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs143949228, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with LRBA-related conditions. ClinVar contains an entry for this variant (Variation ID: 373388). 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. 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. |