Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000547346 | SCV000634150 | benign | Hyper-IgM syndrome type 1 | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781203 | SCV000919089 | benign | not specified | 2018-11-21 | criteria provided, single submitter | clinical testing | Variant summary: CD40LG c.684A>G alters a non-conserved nucleotide resulting in a synonymous change. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0035 in 198835 control chromosomes, predominantly at a frequency of 0.035 within the African subpopulation in the gnomAD database, including 8 homozygotes and 172 hemizygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 22-fold of the estimated maximal expected allele frequency for a pathogenic variant in CD40LG causing Hyper IgM Syndrome Type 1 phenotype (0.0016), while the overall frequency of the variant is approximately 2-fold of the estimated maximal expected allele frequency for a pathogenic variant; these data strongly suggest that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.684A>G in individuals affected with Hyper IgM Syndrome Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. |
Prevention |
RCV003960288 | SCV004780649 | benign | CD40LG-related disorder | 2019-03-13 | criteria provided, single submitter | clinical testing | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |