Submissions for variant NM_002485.5(NBN):c.38-1G>A

dbSNP: rs1812140936

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001174785	SCV001338119	uncertain significance	not specified	2020-01-27	criteria provided, single submitter	clinical testing	Variant summary: NBN c.38-1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: two predict the variant abolishes a 3' acceptor site and generates a novel 3' acceptor site 2 nucleotides downstream, which would result in a frameshift. In addition, 1 computational tool also predicts the activation of a tandem acceptor site, 3 nucleotides downstream of the preferential proximal AG site, which would result in an in-frame deletion of one amino acid from the protein product. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250848 control chromosomes (gnomAD). To our knowledge, no occurrence of c.38-1G>A in individuals affected with Nijmegen Breakage Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.