Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330400 | SCV004039010 | pathogenic | Joubert syndrome and related disorders | 2023-08-10 | criteria provided, single submitter | clinical testing | Variant summary: B9D2 c.301A>C (p.Ser101Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.2e-06 in 244814 control chromosomes. c.301A>C has been reported in the literature in two siblings affected with Meckel Syndrome (example, Dowdle_2011). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in a complete loss of normal activity, as the variant has failed to rescue the developmental deficits of a B9D2 knockout zebrafish, and has failed to interact with MKS1, another key B9 domain-containing protein (Dowdle_2011). These data indicate that the variant is likely to be associated with Joubert Syndrome And Related Disorders. The following publication have been ascertained in the context of this evaluation (PMID: 21763481). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000023919 | SCV000045210 | pathogenic | Meckel syndrome, type 10 | 2011-07-15 | no assertion criteria provided | literature only |