ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.1397+2T>A

dbSNP: rs730881850
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160788 SCV000211451 likely pathogenic not provided 2021-11-11 criteria provided, single submitter clinical testing Canonical splice site variant expected to result in aberrant splicing disrupting the nuclear localization signal motif (Damiola 2014), although in the absence of functional evidence the actual effect of this sequence change is unknown; Not observed at significant frequency in large population cohorts (Lek et al., 2016); Observed in individuals with breast cancer (Susswein 2016); This variant is associated with the following publications: (PMID: 26681312)
Labcorp Genetics (formerly Invitae), Labcorp RCV000459098 SCV000553039 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2024-02-19 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. Variants that disrupt the donor or acceptor splice site 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) 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. 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.
Baylor Genetics RCV003467262 SCV004199701 likely pathogenic Aplastic anemia 2022-12-14 criteria provided, single submitter clinical testing

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