ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1397+2T>A (rs730881850)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160788 SCV000211451 pathogenic not provided 2014-08-25 criteria provided, single submitter clinical testing This pathogenic variant is denoted NBN c.1397+2T>A or IVS10+2T>A and consists of a T>A nucleotide substitution at the +2 position of intron 10 of the NBN gene. The variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has not, to our knowledge, been published in the literature. Based on current evidence, we consider this variant to be pathogenic.
Invitae RCV000459098 SCV000553039 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2020-01-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 10 of the NBN gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with breast cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 182721). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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