Submissions for variant NM_002485.5(NBN):c.2082T>G (p.Pro694=)

gnomAD frequency: 0.02020  dbSNP: rs7823648

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000128893	SCV000172753	benign	Hereditary cancer-predisposing syndrome	2014-11-20	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV000350955	SCV000475287	benign	Microcephaly, normal intelligence and immunodeficiency	2018-01-12	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000350955	SCV000562939	benign	Microcephaly, normal intelligence and immunodeficiency	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001705925	SCV000604435	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000507423	SCV000806427	benign	not specified	2017-02-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000507423	SCV000888333	benign	not specified	2020-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001705925	SCV001916584	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225416	SCV002505276	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315861	SCV004016049	benign	Acute lymphoid leukemia	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001705925	SCV005271443	benign	not provided		criteria provided, single submitter	not provided
True Health Diagnostics	RCV000128893	SCV000788077	likely benign	Hereditary cancer-predisposing syndrome	2017-09-11	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000350955	SCV001456582	benign	Microcephaly, normal intelligence and immunodeficiency	2020-09-16	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000507423	SCV001553554	benign	not specified		no assertion criteria provided	clinical testing	The NBN p.Pro694= variant was not identified in the literature nor was it identified in the Zhejiang Colon Cancer Database. The variant was identified in the following databases: dbSNP (ID: rs7823648) as other, ClinVar (classified as benign by Ambry genetics, Invitae; classified as likely benign by Illumina), and LOVD 3.0. The variant was identified in control databases in 2107 (77 homozygous) of 277000 chromosomes at a frequency of 0.0076 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: African in 1843 of 24028 chromosomes (freq: 0.077). The p.Pro694= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000507423	SCV001809357	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001705925	SCV001965298	likely benign	not provided		no assertion criteria provided	clinical testing