CD70 was first reported in relation to AR immundeficiency and succeptibiltiy to EBV infection and related malignancy in 2017(Iwaza et al., PMID: 28011863). Additional symptoms reporte din humans include Bechet's like syndromes and periodic fever. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism(s) or inheritance pattern. Therefore, the following disease entities have been lumped into one disease entities, (OMIM: 28011863) Multiple variants (missense, frameshift) have been reported in 5 probands in 4 publications (PMIDs: 28011863, 28011864, 29434583, 32849540) are included in this curation. Significant functional testing was done. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is reported to be loss of function of CD70. This gene-disease relationship is also supported by animal models, expression studies, in vitro functional assays, etc.) (PMIDs: 23269247, 28011863, 28011864, 29434583, 32849540). In summary, there is definitive evidence supporting the relationship between CD70 and AR lymphoproliferaiton with immunodeficiency This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.This classification was approved by the ClinGen PIRD GCEP on the meeting date 5/21/24.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.