Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000482820 | SCV000568717 | pathogenic | not provided | 2017-11-24 | criteria provided, single submitter | clinical testing | The c.835_836delAC pathogenic variant in the NCF2 gene has been reported previously in association with chronic granulomatous disease (Noack et al., 1999; Vignesh et al., 2017). The deletion causes a frameshift starting with codon Threonine 279, changes this amino acid to a Glycine residue and creates a premature Stop codon at position 16 of the new reading frame, denoted p.Thr279GlyfsX16. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In summary, we consider this variant to be pathogenic. |
| Labcorp Genetics |
RCV001865445 | SCV002232504 | pathogenic | Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr279Glyfs*16) 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). This premature translational stop signal has been observed in individual(s) with chronic granulomatous disease (PMID: 10598813). ClinVar contains an entry for this variant (Variation ID: 420120). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |