Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000728607 | SCV000856201 | likely pathogenic | not provided | 2017-08-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002536414 | SCV003520263 | likely pathogenic | Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative | 2024-03-27 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 5 (c.288-3_300del) of the CYBA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CYBA are known to be pathogenic (PMID: 10910929, 20167518, 22876374). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has been observed in individual(s) with chronic granulomatous disease (PMID: 20167518). This variant is also known as c.288-6_296del16. ClinVar contains an entry for this variant (Variation ID: 593535). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317353 | SCV004020449 | likely pathogenic | Chronic granulomatous disease | 2023-06-26 | criteria provided, single submitter | clinical testing | Variant summary: CYBA c.288-3_300del16 is located at a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.2e-06 in 160216 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.288-3_300del16 has been reported in the literature in at least one compound heterozygous individual affected with Chronic Granulomatous Disease (e.g., Roos_2010, Roos_2021). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 20167518, 34547651). Two submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |