Submissions for variant NM_024685.4(BBS10):c.1599_1602del (p.Thr534fs)

dbSNP: rs770556842

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169372	SCV000220750	likely pathogenic	Bardet-Biedl syndrome 10	2014-09-29	criteria provided, single submitter	literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001204588	SCV000916669	pathogenic	Bardet-Biedl syndrome	2021-10-17	criteria provided, single submitter	clinical testing	Variant summary: BBS10 c.1599_1602delAACT (p.Thr534IlefsX21) 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 allele was found at a frequency of 7.9e-06 in 251708 control chromosomes. c.1599_1602delAACT has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (example, Alvarez-Satta_2014, Chen_2011, Muller_2010). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae	RCV001204588	SCV001375801	pathogenic	Bardet-Biedl syndrome	2019-08-18	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the BBS10 protein. Other variant(s) that disrupt this region (p.Tyr559*) have been determined to be pathogenic (PMID:20472660, 27788217, 28808579). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has been observed in several individuals affected with Bardet-Biedl syndrome (PMID: 20177705, 24611592, 21642631). ClinVar contains an entry for this variant (Variation ID: 188992). This variant is present in population databases (rs770556842, ExAC 0.001%). This sequence change results in a premature translational stop signal in the BBS10 gene (p.Thr534Ilefs*21). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 190 amino acids of the BBS10 protein.
Revvity Omics, Revvity	RCV000169372	SCV003813640	pathogenic	Bardet-Biedl syndrome 10	2022-10-20	criteria provided, single submitter	clinical testing
SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation	RCV001204588	SCV003915905	pathogenic	Bardet-Biedl syndrome		criteria provided, single submitter	research	This variant was observed in compound heterozygosity with variant NC_000012.11:g.76741496dup
Baylor Genetics	RCV000169372	SCV004217453	pathogenic	Bardet-Biedl syndrome 10	2023-05-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927566	SCV004741395	pathogenic	BBS10-related condition	2023-12-29	criteria provided, single submitter	clinical testing	The BBS10 c.1599_1602delAACT variant is predicted to result in a frameshift and premature protein termination (p.Thr534Ilefs*21). This variant was reported in individuals with Bardet-Biedl syndrome (Muller et al. 2010. PubMed ID: 20177705; Álvarez-Satta et al. 2014. PubMed ID: 24611592; Chen et al. 2011. PubMed ID: 21642631). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. Frameshift variants in BBS10 are expected to be pathogenic. This variant is interpreted as pathogenic.