ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.995-2A>G (rs876659521)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223218 SCV000276088 likely pathogenic Hereditary cancer-predisposing syndrome 2017-11-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (B-level) evidence supporting pathogenicity
Color RCV000223218 SCV000685842 likely pathogenic Hereditary cancer-predisposing syndrome 2018-06-18 criteria provided, single submitter clinical testing
Counsyl RCV000231563 SCV000790071 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2017-03-03 criteria provided, single submitter clinical testing
GeneDx RCV000481197 SCV000565310 likely pathogenic not provided 2017-08-24 criteria provided, single submitter clinical testing This variant is denoted NBN c.995-2A>G or IVS8-2A>G and consists of an A>G nucleotide substitution at the -2 position of intron 8 of the NBN gene. This variant destroys a canonical splice acceptor 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 been reported in at least one individual with ovarian cancer (Ramus 2015). Based on the currently available information, we consider NBN c.995-2A>G to be a likely pathogenic variant.
Invitae RCV000231563 SCV000287490 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2018-11-22 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 8 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 ovarian cancer (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 232050). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.