Submissions for variant NM_002485.5(NBN):c.1914+9C>T

gnomAD frequency: 0.01874  dbSNP: rs13312938

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000119107	SCV000153818	benign	Microcephaly, normal intelligence and immunodeficiency	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000131005	SCV000185931	benign	Hereditary cancer-predisposing syndrome	2012-08-07	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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	RCV000119107	SCV000475291	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.
Color Diagnostics, LLC DBA Color Health	RCV000131005	SCV000685743	benign	Hereditary cancer-predisposing syndrome	2015-04-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000507886	SCV000806423	benign	not specified	2016-11-22	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000507886	SCV000888330	benign	not specified	2020-10-09	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000759170	SCV001157387	benign	not provided	2022-11-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000759170	SCV001883407	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	RCV002225344	SCV002505284	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315698	SCV004016044	benign	Acute lymphoid leukemia	2023-07-07	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000119107	SCV001456587	benign	Microcephaly, normal intelligence and immunodeficiency	2020-09-16	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357373	SCV001552830	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The NBN c.1914+9C>T variant was not identified in the literature nor was it identified in the Cosmic, LOVD 3.0, and Zhejiang Colon Cancer Database. The variant was identified in dbSNP (ID: rs13312938) “With other allele”, ClinVar (benign by Invitae and Ambry Genetics, and likely benign by Illumina), Clinvitae (2x), and in control databases in 1353 (42 homozygous) of 246988 chromosomes at a frequency of 0.005 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017), being identified in the following populations: African in 1230 (41 homozygous) of 21232 chromosomes (frequency: 0.06), Other in 19 of 5832 chromosomes (frequency: 003), Latino in 82 of 32908 chromosomes (frequency: 0.002), European Non-Finnish in 13 of 108340 chromosomes (frequency: 0.0001), East Asian in 1 of 17718 chromosomes (frequency: 0.00006), South Asian in 8 (1 homozygous) of 27888 chromosomes (frequency: 0.0003). The variant occurs outside of the splicing consensus sequence and 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	RCV000507886	SCV001807832	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000507886	SCV001970647	benign	not specified		no assertion criteria provided	clinical testing