ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.550G>T (p.Val184Phe)

dbSNP: rs1554566641
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000636731 SCV000758171 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2022-02-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 184 of the NBN protein (p.Val184Phe). This variant is not present in population databases (gnomAD no frequency). 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: 530734). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV001024208 SCV001186182 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-23 criteria provided, single submitter clinical testing The p.V184F variant (also known as c.550G>T), located in coding exon 5 of the NBN gene, results from a G to T substitution at nucleotide position 550. The valine at codon 184 is replaced by phenylalanine, an amino acid with highly similar properties. 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.
Genome-Nilou Lab RCV000636731 SCV002045178 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000636731 SCV002584756 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2022-07-21 criteria provided, single submitter clinical testing The NBN c.550G>T (p.Val184Phe) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Nijmegan breakage syndrome or NBN-associated cancers. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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