Submissions for variant NM_002485.5(NBN):c.37+11A>G

gnomAD frequency: 0.00540  dbSNP: rs115032431

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000679464	SCV000806436	benign	not specified	2017-03-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001165001	SCV001327164	benign	Microcephaly, normal intelligence and immunodeficiency	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV001644684	SCV001855594	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000679464	SCV002066533	benign	not specified	2018-11-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001165001	SCV002360130	benign	Microcephaly, normal intelligence and immunodeficiency	2025-02-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225674	SCV002505321	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002491152	SCV002800025	benign	Microcephaly, normal intelligence and immunodeficiency; Aplastic anemia; Acute lymphoid leukemia	2021-09-23	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003316754	SCV004016046	benign	Acute lymphoid leukemia	2023-07-07	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355304	SCV001550156	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The NBN c.37+11A>G variant was not identified in the literature nor was it identified in the ClinVar, Cosmic, LOVD 3.0, and Zhejiang Colon Cancer Database. The variant was identified in dbSNP (ID: rs115032431) as “NA”, and in control databases in 425 (3 homozygous) of 272302 chromosomes at a frequency of 0.002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 391 (3 homozygous) of 23526 chromosomes (freq: 0.02), Other in 3 of 6382 chromosomes (freq: 0.0005), Latino in 27 of 34324 chromosomes (freq: 0.0008), European Non-Finnish in 4 of 123086 chromosomes (freq: 0.00003), while not observed in the Ashkenazi Jewish, East Asian, European Finnish, and South Asian populations. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.