ClinVar Miner

Submissions for variant NM_001364905.1(LRBA):c.7364C>G (p.Ala2455Gly)

dbSNP: rs542791563
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000650424 SCV000772269 uncertain significance Combined immunodeficiency due to LRBA deficiency 2023-08-10 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 540400). This variant has not been reported in the literature in individuals affected with LRBA-related conditions. This variant is present in population databases (rs542791563, gnomAD 0.2%). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 2466 of the LRBA protein (p.Ala2466Gly).
Neuberg Centre For Genomic Medicine, NCGM RCV000650424 SCV004171938 uncertain significance Combined immunodeficiency due to LRBA deficiency criteria provided, single submitter clinical testing The missense c.7364C>G(p.Ala2455Gly) variant in LRBA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is reported with an allele frequency of 0.02% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain significance. The amino acid change p.Ala2455Gly in LRBA is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Ala at position 2455 is changed to a Gly changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.