Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000688841 | SCV000816465 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2825 of the LRBA protein (p.Arg2825Trp). This variant is present in population databases (rs143351602, gnomAD 0.2%). 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: 568471). 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 disruptive. 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. |
Center for Genomics, |
RCV000688841 | SCV003920155 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2021-03-30 | criteria provided, single submitter | clinical testing | LRBA NM_006726.4 exon 57 p.Arg2825Trp (c.8473C>T): This variant has not been reported in the literature but is present in 0.1% (45/24964) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/4-151199033-G-A). This variant is present in ClinVar (Variation ID:568471). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Gene |
RCV003332230 | SCV004040112 | uncertain significance | not provided | 2023-03-26 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35753512, 34329649) |