ClinVar Miner

Submissions for variant NM_001364905.1(LRBA):c.6827G>A (p.Arg2276His)

gnomAD frequency: 0.00010  dbSNP: rs200802435
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001038575 SCV001202052 uncertain significance Combined immunodeficiency due to LRBA deficiency 2022-08-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2287 of the LRBA protein (p.Arg2287His). This variant is present in population databases (rs200802435, gnomAD 0.04%). 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: 837277). 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"). 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.
CeGaT Center for Human Genetics Tuebingen RCV001092646 SCV001249254 uncertain significance not provided 2019-07-01 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV001038575 SCV001469026 uncertain significance Combined immunodeficiency due to LRBA deficiency 2020-12-22 criteria provided, single submitter clinical testing This LRBA variant (rs200802435) is rare (<0.1%) in a large population dataset (gnomAD: 40/282366 total alleles; 0.014%; no homozygotes). It has an entry in ClinVar, but has not been reported in the literature in individuals with LRBA-related conditions. Three bioinformatics tools predict that this substitution would be damaging. The arginine residue at this position is strongly conserved across the vertebrate species accessed. This variant is not predicted to affect normal exon 46 splicing, although this has not been confirmed experimentally to our knowledge. This variant alone is not expected to cause CVID8. Due to insufficient evidence, we consider the clinical significance of c.6860G>A to be uncertain at this time.

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