ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.817dup (p.Thr273fs) (rs730881839)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000258971 SCV000211425 pathogenic not provided 2016-11-15 criteria provided, single submitter clinical testing This duplication of one nucleotide in NBN is denoted c.817dupA at the cDNA level and p.Thr273AsnfsX12 (T273NfsX12) at the protein level. The normal sequence, with the base that is duplicated in braces, is TGAT[A]CAGG. The duplication causes a frameshift, which changes a Threonine to an Asparagine at codon 273, and creates a premature stop codon at position 12 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. NBN c.817dupA was identified in at least one individual with breast cancer (Susswein 2015). We consider this variant to be likely pathogenic.
Ambry Genetics RCV000160766 SCV000277110 pathogenic Hereditary cancer-predisposing syndrome 2015-07-09 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000160766 SCV001345868 pathogenic Hereditary cancer-predisposing syndrome 2019-12-20 criteria provided, single submitter clinical testing
Invitae RCV001226188 SCV001398490 pathogenic Microcephaly, normal intelligence and immunodeficiency 2019-11-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr273Asnfs*12) 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 been observed in individual(s) with breast cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 182702). 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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