ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.1471G>A (p.Glu491Lys)

gnomAD frequency: 0.00001  dbSNP: rs776900339
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482670 SCV000567168 uncertain significance not provided 2019-04-15 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016)
Labcorp Genetics (formerly Invitae), Labcorp RCV000546529 SCV000634230 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 491 of the NBN protein (p.Glu491Lys). This variant is present in population databases (rs776900339, gnomAD 0.007%). 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: 419397). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Mendelics RCV000546529 SCV000838301 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2018-07-02 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000546529 SCV002044616 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002395149 SCV002697969 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-25 criteria provided, single submitter clinical testing The p.E491K variant (also known as c.1471G>A), located in coding exon 11 of the NBN gene, results from a G to A substitution at nucleotide position 1471. The glutamic acid at codon 491 is replaced by lysine, an amino acid with similar properties. This amino acid position is well 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.
Baylor Genetics RCV004568163 SCV005056208 uncertain significance Aplastic anemia 2023-11-20 criteria provided, single submitter clinical testing
Natera, Inc. RCV000546529 SCV001456597 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2020-09-16 no assertion criteria provided clinical testing

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