Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000234855 | SCV001575976 | likely pathogenic | Autosomal recessive severe congenital neutropenia due to CSF3R deficiency | 2018-02-15 | criteria provided, single submitter | clinical testing | Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CSF3R are known to be pathogenic (PMID: 24753537, 26324699). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with severe congenital neutropenia (PMID: 26324699). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 242835). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 8 of the CSF3R gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. 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. |
| OMIM | RCV000234855 | SCV000292051 | pathogenic | Autosomal recessive severe congenital neutropenia due to CSF3R deficiency | 2016-07-05 | no assertion criteria provided | literature only |