Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000668190 | SCV000792752 | likely pathogenic | Bardet-Biedl syndrome 2 | 2017-07-12 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001069811 | SCV001235008 | pathogenic | Bardet-Biedl syndrome | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Met637Glufs*12) in the BBS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS2 are known to be pathogenic (PMID: 11285252, 20177705, 24608809, 26518167). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (PMID: 15666242). ClinVar contains an entry for this variant (Variation ID: 552850). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Blueprint Genetics | RCV001074318 | SCV001239891 | likely pathogenic | Retinal dystrophy | 2019-06-29 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001069811 | SCV001478761 | likely pathogenic | Bardet-Biedl syndrome | 2021-01-29 | criteria provided, single submitter | clinical testing | Variant summary: BBS2 c.1909_1910delAT (p.Met637GlufsX12) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251460 control chromosomes. c.1909_1910delAT has been reported in the literature as compound heterozygous with another pathogenic variant in a fetus affected with Bardet-Biedl Syndrome (e.g. Karmous-Benailly_2005). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories cited the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |