Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001005004 | SCV001164565 | uncertain significance | Retinitis pigmentosa 74 | 2018-12-03 | criteria provided, single submitter | research | The heterozygous p.Leu221Pro variant in BBS2 was identified by our study in the compound heterozygous state, with a likely pathogenic variant, in one individual with retinitis pigmentosa. The presence of this variant in combination with a likely pathogenic variant increases the likelihood that the p.Leu221Pro variant is pathogenic. The p.Leu221Pro variant in BBS2 has not been previously reported in individuals with Retinitis Pigmentosa and was absent from large population studies. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinial significance of the p.Leu221Pro variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PM3_Supporting (Richards 2015). |
Invitae | RCV001862747 | SCV002260833 | uncertain significance | Bardet-Biedl syndrome | 2022-03-09 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 221 of the BBS2 protein (p.Leu221Pro). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 814000). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 20177705). This variant is not present in population databases (gnomAD no frequency). |
Fulgent Genetics, |
RCV002489516 | SCV002800904 | uncertain significance | Bardet-Biedl syndrome 2; Retinitis pigmentosa 74 | 2021-10-28 | criteria provided, single submitter | clinical testing | |
New York Genome Center | RCV002489516 | SCV003925447 | uncertain significance | Bardet-Biedl syndrome 2; Retinitis pigmentosa 74 | 2022-04-06 | criteria provided, single submitter | clinical testing |