ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.1520A>G (p.His507Arg)

dbSNP: rs587782520
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131697 SCV000186734 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-10 criteria provided, single submitter clinical testing The p.H507R variant (also known as c.1520A>G), located in coding exon 11 of the NBN gene, results from an A to G substitution at nucleotide position 1520. The histidine at codon 507 is replaced by arginine, an amino acid with highly similar properties. This alteration was detected on a 25-gene panel test in a woman who was diagnosed with breast cancer before age 50 (Tung N et al. Cancer, 2015 Jan;121:25-33). 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.
Counsyl RCV000669514 SCV000794272 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2017-10-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000669514 SCV001205587 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2024-10-14 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 507 of the NBN protein (p.His507Arg). This variant is present in population databases (rs587782520, gnomAD 0.0009%). 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: 142521). 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. 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 RCV001561788 SCV001784450 uncertain significance not provided 2020-06-22 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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 RCV000669514 SCV002044604 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000131697 SCV002536607 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-04 criteria provided, single submitter curation
Fulgent Genetics, Fulgent Genetics RCV005042273 SCV005674440 uncertain significance Microcephaly, normal intelligence and immunodeficiency; Aplastic anemia; Acute lymphoid leukemia 2024-05-31 criteria provided, single submitter clinical testing
Natera, Inc. RCV000669514 SCV002078561 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2020-08-27 no assertion criteria provided clinical testing

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