Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001236992 | SCV001409735 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2020-02-05 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 11 of the NBN gene. It does not directly change the encoded amino acid sequence of the NBN protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). This variant has not been reported in the literature in individuals with NBN-related conditions. |
Ambry Genetics | RCV002411875 | SCV002716439 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-30 | criteria provided, single submitter | clinical testing | The c.1846-3T>C intronic variant results from a T to C substitution 3 nucleotides upstream from coding exon 12 in the NBN gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |