ClinVar Miner

Submissions for variant NM_001024688.2(NBN):c.-59del (rs876659592)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221586 SCV000276222 pathogenic Hereditary cancer-predisposing syndrome 2015-06-01 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000636697 SCV000758137 pathogenic Microcephaly, normal intelligence and immunodeficiency 2019-05-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile63Thrfs*4) in the NBN gene. It is expected to result in an absent or disrupted protein product. 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. ClinVar contains an entry for this variant (Variation ID: 232165). Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000657396 SCV000779129 pathogenic not provided 2017-10-17 criteria provided, single submitter clinical testing This deletion of one nucleotide in NBN is denoted c.188delT at the cDNA level and p.Ile63ThrfsX4 (I63TfsX4) at the protein level. The normal sequence, with the base that is deleted in brackets, is GAAA[delT]CCCT. The deletion causes a frameshift which changes an Isoleucine to a Threonine at codon 63, and creates a premature stop codon at position 4 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.

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