ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.2119_2141del (p.Asp707fs) (rs1554555782)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000636703 SCV000758143 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2017-12-08 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the NBN gene (p.Asp707Lysfs*27). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acids of the NBN protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NBN-related disease. This variant is expected to disrupt the entire ATM interaction domain (amino acids 734-754) of the NBN protein (PMID: 24894818, 21035407), which is important for activating ATM in the double-strand break repair pathway (PMID: 15964794, 15048089). 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.

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. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.