ClinVar Miner

Submissions for variant NM_000074.2(CD40LG):c.322_325delGAAA (rs1569376930)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000689441 SCV000817092 likely pathogenic X-linked hyper-IgM syndrome 2018-05-11 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the CD40LG gene (p.Glu108Thrfs*19). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 154 amino acids of the CD40LG protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CD40LG-related disease. A different variant (c.326delA) giving rise to similar frameshift observed here (p.Asn109Thrfs*19) has been reported in an individual affected with hyper IgM syndrome (PMID: 20591076). This variant is reported in the literature as c.323delA (p.E108fs*19). The p.Thr254 amino acid residue in CD40LG has been determined to be clinically significant (PMID: 10484640, 22678466, 25541662). This suggests that variants that disrupt this residue are likely to be causative of disease. 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.

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