ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.2141G>A (p.Arg714Gln)

gnomAD frequency: 0.00002  dbSNP: rs753270166
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000526011 SCV000634277 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2024-11-04 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 714 of the NBN protein (p.Arg714Gln). This variant is present in population databases (rs753270166, gnomAD 0.006%). 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: 461541). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". 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 RCV000569966 SCV000662678 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-12 criteria provided, single submitter clinical testing The p.R714Q variant (also known as c.2141G>A), located in coding exon 14 of the NBN gene, results from a G to A substitution at nucleotide position 2141. The arginine at codon 714 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, glutamine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001561929 SCV001784618 uncertain significance not provided 2023-04-28 criteria provided, single submitter clinical testing 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
Genome-Nilou Lab RCV000526011 SCV002046049 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV003470739 SCV004199498 uncertain significance Aplastic anemia 2023-10-26 criteria provided, single submitter clinical testing
Natera, Inc. RCV000526011 SCV001456580 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2020-09-16 no assertion criteria provided clinical testing

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