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 2021-01-14 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016) This variant is associated with the following publications: (PMID: 25677497)
Counsyl RCV000170448 SCV000486381 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2016-05-19 criteria provided, single submitter clinical testing
Color Health, Inc RCV000446931 SCV000537672 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Invitae RCV000170448 SCV000553057 pathogenic Microcephaly, normal intelligence and immunodeficiency 2020-10-08 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 The p.Q344* pathogenic mutation (also known as c.1030C>T), located in coding exon 9 of the NBN gene, results from a C to T substitution at nucleotide position 1030. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This mutation has been reported in conjunction with a second NBN mutation in an individual with Nijmegen breakage syndrome (Patel et al. J. Clin. Immunol. 2015; 35 (2): 227-33). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
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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