Submissions for variant NM_002485.5(NBN):c.584+9T>C

gnomAD frequency: 0.00003  dbSNP: rs746913991

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000443854	SCV000513856	likely benign	not specified	2016-04-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001083819	SCV000562960	likely benign	Microcephaly, normal intelligence and immunodeficiency	2022-10-30	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000459632	SCV001134514	likely benign	not provided	2018-11-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000443854	SCV001338406	uncertain significance	not specified	2022-08-17	criteria provided, single submitter	clinical testing	Variant summary: NBN c.584+9T>C alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.4e-05 in 250980 control chromosomes, exclusively within the Non-Finnish European subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.584+9T>C in individuals affected with Nijmegen Breakage Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Genome-Nilou Lab	RCV001083819	SCV002045960	likely benign	Microcephaly, normal intelligence and immunodeficiency	2021-11-07	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000443854	SCV002066705	likely benign	not specified	2020-12-03	criteria provided, single submitter	clinical testing