ClinVar Miner

Submissions for variant NM_000433.4(NCF2):c.257+1G>A

dbSNP: rs990043411
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412920 SCV000490660 pathogenic not provided 2015-06-29 criteria provided, single submitter clinical testing The c.257+1 G>A splice site variant in the NCF2 gene destroys the canonical splice donor site in intron 2. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.257+1 G>A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret c.257+1 G>A as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001861411 SCV002250538 likely pathogenic Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 2023-06-17 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 372431). This variant has not been reported in the literature in individuals affected with NCF2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 2 of the NCF2 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 NCF2 are known to be pathogenic (PMID: 10498624, 20167518).

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