ClinVar

Description

This variant is a gross deletion of the genomic region encompassing exon(s) 4-5 of the CD40LG gene. The 5' boundary is likely confined to intron 3. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. This variant has not been reported in the literature in individuals affected with CD40LG-related conditions. This variant disrupts the p.Ala123 amino acid residue in CD40LG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8094231, 10559240, 15623492). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.