Submissions for variant NM_002485.5(NBN):c.105T>G (p.Ile35Met)

dbSNP: rs78870221

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000216738	SCV000277981	likely benign	Hereditary cancer-predisposing syndrome	2022-12-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000533679	SCV000634195	uncertain significance	Microcephaly, normal intelligence and immunodeficiency	2024-01-22	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 35 of the NBN protein (p.Ile35Met). This variant is present in population databases (rs78870221, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with NBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 233580). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
GeneDx	RCV001570359	SCV001794639	uncertain significance	not provided	2019-12-24	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this 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: 31278556)
Genome-Nilou Lab	RCV000533679	SCV002045284	uncertain significance	Microcephaly, normal intelligence and immunodeficiency	2021-11-07	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003475034	SCV004199586	uncertain significance	Aplastic anemia	2024-03-24	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000533679	SCV001461783	uncertain significance	Microcephaly, normal intelligence and immunodeficiency	2020-09-16	no assertion criteria provided	clinical testing