ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.2194C>T (p.Gln732Ter) (rs1554554265)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000552881 SCV000634282 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2017-01-31 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the NBN mRNA at codon 732 (p.Gln732*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 23 amino acid residues of the NBN protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an NBN-related disease. This truncating variant removes the 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, this is a novel truncation that deletes an important protein domain. In the absence of segregation or functional data, it has been classified as Likely Pathogenic.

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