ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1903A>T (p.Lys635Ter) (rs587782545)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131755 SCV000186798 pathogenic Hereditary cancer-predisposing syndrome 2017-12-04 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)
GeneDx RCV000219708 SCV000279419 pathogenic not provided 2018-04-19 criteria provided, single submitter clinical testing This pathogenic variant is denoted NBN c.1903A>T at the cDNA level and p.Lys635Ter (K635X) at the protein level. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in an individual with breast cancer and in an individual with pancreatic cancer (Walsh 2017, Lowery 2018). We consider NBN Lys635Ter to be pathogenic.
Invitae RCV000227700 SCV000287457 pathogenic Microcephaly, normal intelligence and immunodeficiency 2018-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys635*) in the NBN gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs587782545, ExAC 0.01%). This variant has been reported in an individual undergoing hereditary cancer multigene panel testing (PMID: 24763289). ClinVar contains an entry for this variant (Variation ID: 142559). Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000227700 SCV000486262 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2016-04-25 criteria provided, single submitter clinical testing
Color RCV000131755 SCV000537637 pathogenic Hereditary cancer-predisposing syndrome 2016-02-22 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763606 SCV000894452 pathogenic Microcephaly, normal intelligence and immunodeficiency; Aplastic anemia; Acute lymphoid leukemia 2018-10-31 criteria provided, single submitter clinical testing

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