ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.706A>G (p.Lys236Glu)

dbSNP: rs1060503482
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000468446 SCV000553100 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2023-09-15 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 411778). This missense change has been observed in individual(s) with breast cancer, bone marrow failure and/or myelodysplastic syndrome (PMID: 25239263, 35039564). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 236 of the NBN protein (p.Lys236Glu).
Ambry Genetics RCV000569502 SCV000670277 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-23 criteria provided, single submitter clinical testing The p.K236E variant (also known as c.706A>G), located in coding exon 7 of the NBN gene, results from an A to G substitution at nucleotide position 706. The lysine at codon 236 is replaced by glutamic acid, an amino acid with similar properties. In a study of patients with idiopathic bone marrow failure or myelodysplastic syndrome, this variant was seen in an 18-year-old male with bone marrow failure (Zhang MY et al. Haematologica. 2015 Jan;100:42-8)This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx RCV001575608 SCV001802640 uncertain significance not provided 2019-06-14 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 25239263)
Genome-Nilou Lab RCV000468446 SCV002044806 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000569502 SCV002536708 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-16 criteria provided, single submitter curation

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.