Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001240485 | SCV001413431 | pathogenic | Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative | 2023-11-15 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 4 of the CYBA gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs747774702, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with clinical features of chronic granulomatous disease (PMID: 1415254, 20167518, 22924696, 27537055). ClinVar contains an entry for this variant (Variation ID: 965927). Studies have shown that disruption of this splice site alters CYBA gene expression (PMID: 1415254). Studies have shown that disruption of this splice site results in skipping of exon 4, but is expected to preserve the integrity of the reading-frame (PMID: 1415254). 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. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV001240485 | SCV002797710 | pathogenic | Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative | 2022-03-31 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001828951 | SCV002089435 | likely pathogenic | Chronic granulomatous disease | 2020-07-09 | no assertion criteria provided | clinical testing |