Submissions for variant NM_002485.5(NBN):c.266G>A (p.Arg89Gln)

dbSNP: rs747315554

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000204158	SCV000262164	uncertain significance	Microcephaly, normal intelligence and immunodeficiency	2023-12-22	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 89 of the NBN protein (p.Arg89Gln). This variant is present in population databases (rs747315554, gnomAD 0.007%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 221045). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV000215544	SCV000277769	likely benign	Hereditary cancer-predisposing syndrome	2018-01-15	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Counsyl	RCV000204158	SCV000789454	uncertain significance	Microcephaly, normal intelligence and immunodeficiency	2017-02-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000204158	SCV000838318	uncertain significance	Microcephaly, normal intelligence and immunodeficiency	2018-07-02	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000204158	SCV002045979	uncertain significance	Microcephaly, normal intelligence and immunodeficiency	2021-11-07	criteria provided, single submitter	clinical testing
GeneDx	RCV002466468	SCV002762335	uncertain significance	not provided	2022-12-02	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27149842, 24894818)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV002466468	SCV002774660	uncertain significance	not provided	2022-07-09	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000215544	SCV002819166	uncertain significance	Hereditary cancer-predisposing syndrome	2022-08-18	criteria provided, single submitter	clinical testing