Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001024591 | SCV001186627 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-03-13 | criteria provided, single submitter | clinical testing | The c.584+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 5 in the NBN gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Invitae | RCV001004533 | SCV001382633 | likely pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2019-09-30 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 5 of the NBN gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with NBN-related conditions. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Genome- |
RCV001004533 | SCV002045363 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003467575 | SCV004199689 | likely pathogenic | Aplastic anemia | 2023-03-10 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001004533 | SCV001163583 | likely pathogenic | Microcephaly, normal intelligence and immunodeficiency | no assertion criteria provided | clinical testing |