ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.832T>G (p.Ser278Ala) (rs1225178489)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000589829 SCV000697981 uncertain significance not provided 2016-01-25 criteria provided, single submitter clinical testing Variant summary: The c.832T>G in NBN gene is a missense variant that involves a non-conserved nucleotide and 3/5 in silico tools predict benign outcome. The variant is absent from the broad control population datasets from ExAC, suggesting this variant is not a common polymorphism. The variant has been reported as a germline mutation in one patient presented with a clinical characteristics suggestive of Lynch Syndrome. Ser278 is a direct substrate for ATM kinase, however, the effect of phosphorylation or lack thereof in the functional studies performed in vitro and in vivo showed contradicting results, perhaps, due to limitations of the technical approaches. It is possible, that the variant of interest is a mild mutation and may play role in radiation dose dependency. However further investigation is needed to support this proposition. The variant of interest has not been reported by reputable databases/clinical laboratories. Taken together, the variant was classified as Variant of Uncertain until more information becomes available.
Invitae RCV000701071 SCV000829854 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces serine with alanine at codon 278 of the NBN protein (p.Ser278Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NBN-related disease. ClinVar contains an entry for this variant (Variation ID: 496166). Experimental studies using mice carrying this variant in a homozygous state and human cells transfected with this variant provide insufficient evidence to determine whether this variant affects the function of the NBN protein to a clinically significant degree (PMID: 10839544, 21664921). 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.
Color RCV000772494 SCV000905673 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-08 criteria provided, single submitter clinical testing

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