Submissions for variant NM_000101.4(CYBA):c.268C>G (p.Arg90Gly)

dbSNP: rs179363892

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002036378	SCV002313253	likely pathogenic	Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	2023-07-22	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg90 amino acid residue in CYBA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10910929, 20167518). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1522930). This missense change has been observed in individuals with chronic granulomatous disease (PMID: 20167518, 26185101; Invitae). This variant is present in population databases (rs179363892, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 90 of the CYBA protein (p.Arg90Gly).
PreventionGenetics, part of Exact Sciences	RCV003893090	SCV004712667	pathogenic	CYBA-related disorder	2024-01-11	no assertion criteria provided	clinical testing	The CYBA c.268C>G variant is predicted to result in the amino acid substitution p.Arg90Gly. This variant has been reported reported in homozygous and compound heterozygous states in individuals with chronic granulomatous disease (Roos et al. 2010. PubMed ID: 20167518; de Oliveira-Junior et al. 2015. PubMed ID: 26185101). In addition, other variants impacting this same amino acid have been reported as causative for chronic granulomatous disease [c.268C>T (p.Arg90Trp), c.269G>A (p.Arg90Gln, and c.269G>C (p.Arg90Pro); Rae et al. 2000. PubMed ID: 10910929; Roos et al. 2010. PubMed ID: 20167518; Kulkarni et al. 2018. PubMed ID: 30470980]. This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as pathogenic.