Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001202522 | SCV001373635 | uncertain significance | Bardet-Biedl syndrome | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 794 of the BBS9 protein (p.Asn794Ser). This variant is present in population databases (rs774701632, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with BBS9-related conditions. ClinVar contains an entry for this variant (Variation ID: 934179). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BBS9 protein function with a negative predictive value of 80%. 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. |
Fulgent Genetics, |
RCV002484085 | SCV002787231 | uncertain significance | Bardet-Biedl syndrome 9 | 2022-02-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003346356 | SCV004052771 | uncertain significance | Inborn genetic diseases | 2023-08-15 | criteria provided, single submitter | clinical testing | The c.2381A>G (p.N794S) alteration is located in exon 21 (coding exon 20) of the BBS9 gene. This alteration results from a A to G substitution at nucleotide position 2381, causing the asparagine (N) at amino acid position 794 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Prevention |
RCV003405384 | SCV004107847 | uncertain significance | BBS9-related condition | 2024-01-02 | criteria provided, single submitter | clinical testing | The BBS9 c.2381A>G variant is predicted to result in the amino acid substitution p.Asn794Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.052% of alleles in individuals of Latino descent in gnomAD, which may be too common to be the primary cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |