ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.105_135del (p.Ile35fs) (rs730881840)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160767 SCV000211426 pathogenic not provided 2015-05-01 criteria provided, single submitter clinical testing This deletion of 31 nucleotides in NBN is denoted c.105_135del31 at the cDNA level and p.Ile35MetfsX4 (I35MfsX4) at the protein level. The surrounding sequence is TGAT[del31]GCTG. The deletion causes a frameshift, which changes an Isoleucine to a Methionine at codon 35, and creates a premature stop codon at position 4 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Counsyl RCV000664795 SCV000788810 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2016-12-16 criteria provided, single submitter clinical testing
Invitae RCV000664795 SCV000825843 pathogenic Microcephaly, normal intelligence and immunodeficiency 2019-11-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile35Metfs*4) in the NBN gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with NBN-related disease. ClinVar contains an entry for this variant (Variation ID: 182703). Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). For these reasons, this variant has been classified as Pathogenic.
Color RCV001180837 SCV001345869 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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