ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.949A>G (p.Met317Val)

gnomAD frequency: 0.00002  dbSNP: rs587782502
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131642 SCV000186668 likely benign Hereditary cancer-predisposing syndrome 2019-01-29 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 RCV000477065 SCV000553110 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2024-08-05 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 317 of the NBN protein (p.Met317Val). This variant is present in population databases (rs587782502, gnomAD 0.003%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 142497). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The valine 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.
GeneDx RCV000485286 SCV000565990 uncertain significance not provided 2023-08-02 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; This variant is associated with the following publications: (PMID: 27050099, 26315354, 33471991, 24894818)
Genome-Nilou Lab RCV000477065 SCV002045944 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000131642 SCV002536731 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-04 criteria provided, single submitter curation

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