Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000195535 | SCV000253707 | likely pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2015-03-24 | criteria provided, single submitter | clinical testing | This sequence change is a gross deletion of the genomic region encompassing exons 15-16 of the NBN gene. This deletion extends to both edges of the assayed region, and the 5' and 3' boundaries of this event are not known. While this particular variant has not been reported in the literature, truncating sequence changes in NBN are known to be pathogenic (PMID: 9590180, 16415040). Deletion of exons 15-16 will result in the loss of amino acids 729-754 of the NBN protein, including the termination codon, and is expected to result in an absent or disrupted protein product. This deletion will also lead to the loss of the ATM interaction domain (amino acids 734-754) of the NBN protein (PMID: 24894818, 21035407), which has been shown to be important for activating ATM (PMID: 15064416, 15790808). For these reasons, this variant has been classified as Likely Pathogenic. |