ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.783T>G (p.Asn261Lys)

gnomAD frequency: 0.00001  dbSNP: rs375336614
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000216808 SCV000279707 uncertain significance not provided 2015-12-18 criteria provided, single submitter clinical testing This variant is denoted NBN c.783T>G at the cDNA level, p.Asn261Lys (N261K) at the protein level, and results in the change of an Asparagine to a Lysine (AAT>AAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NBN Asn261Lys was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Asparagine and Lysine differ in some properties, this is considered a semi-conservative amino acid substitution. NBN Asn261Lys occurs at a position that is not conserved and is located in the region of interaction with MTOR, MAPKAP1 and RICTOR, and mediates interaction with SP100 (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether NBN Asn261Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000532301 SCV000634329 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2023-08-23 criteria provided, single submitter clinical testing 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 234702). This variant has not been reported in the literature in individuals affected with NBN-related conditions. This variant is present in population databases (rs375336614, gnomAD 0.002%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 261 of the NBN protein (p.Asn261Lys).
Ambry Genetics RCV000565009 SCV000670193 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-12 criteria provided, single submitter clinical testing The p.N261K variant (also known as c.783T>G), located in coding exon 7 of the NBN gene, results from a T to G substitution at nucleotide position 783. The asparagine at codon 261 is replaced by lysine, an amino acid with similar properties. This amino acid position is poorly conserved in available 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.
Genome-Nilou Lab RCV000532301 SCV002044791 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Natera, Inc. RCV000532301 SCV001460730 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2020-09-16 no assertion criteria provided clinical testing

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