ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.175C>T (p.Gln59Ter) (rs1554568427)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000586448 SCV000697953 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-06 criteria provided, single submitter clinical testing Variant summary: The c.175C>T (p.Gln59*) variant in NBN gene is a nonsense change that results in the loss of the 696 amino acids of NBN (~90%). This change is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is absent from control dataset of ExAC and has not, to our knowledge, been reported in affected individuals via published reports or cited by a reputable database/clinical laboratory. Biallelic truncating mutations in NBN are associated with Nijmegen breakage syndrome whereas heterozygous carriers of a truncated variant have an increased cancer risk. Taking together, the variant was classified as Likely Pathogenic.
Invitae RCV000688264 SCV000815869 pathogenic Microcephaly, normal intelligence and immunodeficiency 2018-05-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln59*) 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. Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). For these reasons, this variant has been classified as Pathogenic.

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