ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1030C>T (rs767215758)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000220210 SCV000279456 pathogenic not provided 2018-02-27 criteria provided, single submitter clinical testing This pathogenic variant is denoted NBN c.1030C>T at the cDNA level and p.Gln344Ter (Q344X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. NBN Gln344Ter has been observed in a compound heterozygous state in a child with Nijmegen Breakage Syndrome (Patel 2015) and is considered pathogenic.
Counsyl RCV000170448 SCV000486381 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2016-05-19 criteria provided, single submitter clinical testing
Color RCV000446931 SCV000537672 pathogenic Hereditary cancer-predisposing syndrome 2015-05-18 criteria provided, single submitter clinical testing
Invitae RCV000170448 SCV000553057 pathogenic Microcephaly, normal intelligence and immunodeficiency 2018-10-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln344*) in the NBN gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs767215758, ExAC 0.009%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with Nijmegen breakage syndrome (PMID: 25677497). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 190229). Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000446931 SCV000662663 pathogenic Hereditary cancer-predisposing syndrome 2017-09-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Fulgent Genetics,Fulgent Genetics RCV000763607 SCV000894453 pathogenic Microcephaly, normal intelligence and immunodeficiency; Aplastic anemia; Acute lymphoid leukemia 2018-10-31 criteria provided, single submitter clinical testing
Innovations Lab, Hyderabad,Tata Consultancy Services Ltd RCV000170448 SCV000196641 pathogenic Microcephaly, normal intelligence and immunodeficiency no assertion criteria provided research Exome sequencing of DNA from an infant and his parents was performed. Genomic analysis revealed deleterious variants in the NBN gene. Confirmatory testing included Sanger sequencing and immunoblotting and radiosensitivity testing of patient lymphocytes.

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