Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781202 | SCV000919088 | likely pathogenic | Hyper-IgM syndrome type 1 | 2018-05-25 | criteria provided, single submitter | clinical testing | Variant summary: CD40LG c.288+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 5' splicing donor site. These predictions are supported by functional studies showing that the variant causes either the skipping of exon 2 or the inclusion of 19 nucleotides due to the use of a cryptic splice site (Nonoyama_1997). The variant was absent in 178146 control chromosomes. c.288+1G>A has been reported in the literature in individuals affected with Hyper IgM Syndrome Type 1. These data indicate that the variant may be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Pediatric Infectious Diseases and Immunodeficiencies Unit |
RCV003493731 | SCV004023240 | pathogenic | Common variable immunodeficiency | no assertion criteria provided | clinical testing | We found the c.288+1G>A variant in an adult female patient with common variable immunodeficiency (CVID). The variant is absent from large population studies. It causes two aberrantly spliced transcripts: one lacking exon 2 (exon 2 skipping) and one with partial intron 2 retention (19bp). This is consistent with the previously reported effect of this variant (PMIDs: 9150729, 15358621, 9746782). The patient had skewed X chromosome inactivation in which the mutated allele is predominantly expressed. Therefore, we classified the variant as Pathogenic. |