Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331828 | SCV004037685 | pathogenic | Chronic granulomatous disease | 2023-08-29 | criteria provided, single submitter | clinical testing | Variant summary: NCF2 c.1099C>T (p.Gln367X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, a commonly known mechanism for disease. The variant was absent in 251064 control chromosomes (gnomAD). c.1099C>T has been reported in the literature in at least one individual affected with Chronic Granulomatous Disease (e.g. Vignesh_2017) . This suggests the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 28035544). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV003497992 | SCV004293855 | pathogenic | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 | 2023-04-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with chronic granulomatous disease (PMID: 20167518, 28035544). This sequence change creates a premature translational stop signal (p.Gln367*) in the NCF2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NCF2 are known to be pathogenic (PMID: 10498624, 20167518). This variant is not present in population databases (gnomAD no frequency). |