Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001897038 | SCV002169017 | pathogenic | Hyper-IgM syndrome type 1 | 2021-07-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 8550833). Disruption of this splice site has been observed in individuals with hyper IgM syndrome. (PMID: 7907793, 8550833, 9150729). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 4 of the CD40LG gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. |