Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000411476 | SCV000486755 | likely pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2016-08-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000411476 | SCV000813855 | likely pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2022-07-11 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 371225). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with NBN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 of the NBN gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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). |
| Ambry Genetics | RCV002365446 | SCV002666567 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-08-11 | criteria provided, single submitter | clinical testing | The c.702+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 6 of the NBN gene. This alteration has been reported with a carrier frequency of 0.0000 in 7051 unselected breast cancer patients and 0.0009 in 11241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun. 2018 10;9:4083). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. 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. |
| Laboratory for Genotyping Development, |
RCV003168594 | SCV002758061 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |