ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.254A>G (p.Asn85Ser) (rs587780095)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115791 SCV000149700 uncertain significance not provided 2014-12-15 criteria provided, single submitter clinical testing This variant is denoted NBN c.254A>G at the cDNA level, p.Asn85Ser (N85S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NBN Asn85Ser was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Asparagine and Serine share similar properties, this is considered a conservative amino acid substitution. NBN Asn85Ser occurs at a position that is moderately conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether NBN Asn85Ser is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000214236 SCV000273223 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-29 criteria provided, single submitter clinical testing The p.N85S variant (also known as c.254A>G), located in coding exon 3 of the NBN gene, results from an A to G substitution at nucleotide position 254. The asparagine at codon 85 is replaced by serine, an amino acid with highly similar properties. In one study of 57 patients with cutaneous melanoma and a history of two or more additional non-cutaneous primary cancers, this variant was seen in 0/57 cases but was reported in 1/1358 controls (Pritchard AL et al. PLoS ONE. 2018 Apr;13:e0194098). In another study, this variant was not observed in 7051 Japanese females with breast cancer, 53 male breast cancer cases, or 11241 female controls; however, it was observed in 1/12490 male controls (Momozawa Y et al. Nat Commun. 2018 Oct;9:4083). This amino acid position is not 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.
Invitae RCV000231493 SCV000287467 likely benign Microcephaly, normal intelligence and immunodeficiency 2020-11-05 criteria provided, single submitter clinical testing
Color Health, Inc RCV000214236 SCV000902943 likely benign Hereditary cancer-predisposing syndrome 2016-10-14 criteria provided, single submitter clinical testing
Natera, Inc. RCV000231493 SCV001461778 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2020-09-16 no assertion criteria provided clinical testing

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