ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.1594G>A (p.Val532Met)

dbSNP: rs545435120
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484172 SCV000566267 uncertain significance not provided 2023-06-14 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; Not observed in any cases, but was observed in unaffected controls from a breast study (Dorling et al., 2021); This variant is associated with the following publications: (PMID: 33471991)
Labcorp Genetics (formerly Invitae), Labcorp RCV000550537 SCV000634239 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2022-09-28 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 532 of the NBN protein (p.Val532Met). This variant is present in population databases (rs545435120, gnomAD 0.01%). 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: 418889). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine 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 RCV001012314 SCV001172747 likely benign Hereditary cancer-predisposing syndrome 2024-03-27 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.
Genome-Nilou Lab RCV000550537 SCV002044588 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001012314 SCV002536610 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-08 criteria provided, single submitter curation

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