ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.804_805GT[2] (p.Val270fs) (rs786202490)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165330 SCV000216053 pathogenic Hereditary cancer-predisposing syndrome 2018-09-18 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000205978 SCV000260006 pathogenic Microcephaly, normal intelligence and immunodeficiency 2019-11-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val270Cysfs*2) 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. ClinVar contains an entry for this variant (Variation ID: 185833). Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000480505 SCV000569057 pathogenic not provided 2018-10-29 criteria provided, single submitter clinical testing This deletion of two nucleotides in NBN is denoted c.808_809delGT at the cDNA level and p.Val270CysfsX2 (V270CfsX2) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GTGT[delGT]TGTT. The deletion causes a frameshift, which changes a Valine to a Cysteine at codon 270 and creates a premature stop codon at position 2 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.808_809delGT, also described as NBN c.804delGT using alternate nomenclature, has been reported in an individual with breast cancer as well as in an unaffected control individual in an ovarian cancer case-control meta-analysis (Damiola 2014, Ramus 2015). We consider this variant to be pathogenic.
Color RCV000165330 SCV000685829 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000480505 SCV001134521 pathogenic not provided 2019-02-20 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity.

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