Submissions for variant NM_024685.4(BBS10):c.1677del (p.Ser558_Tyr559insTer)

gnomAD frequency: 0.00002  dbSNP: rs1555202584

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586002	SCV000699622	pathogenic	Bardet-Biedl syndrome	2023-02-24	criteria provided, single submitter	clinical testing	Variant summary: BBS10 c.1677delC (p.Tyr559X) 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 in HGMD, ClinVar or our laboratory. The variant allele was found at a frequency of 4e-06 in 251022 control chromosomes. c.1677delC has been reported in the literature in individuals affected with Bardet-Biedl Syndrome. These data indicate that the variant may be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
MAGI'S LAB - Medical Genetics Laboratory, MAGI GROUP	RCV000586002	SCV000897984	pathogenic	Bardet-Biedl syndrome	2018-10-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003392426	SCV004120657	pathogenic	BBS10-related condition	2023-06-29	criteria provided, single submitter	clinical testing	The BBS10 c.1677delC variant is predicted to result in premature protein termination (p.Tyr559*). This variant has been reported to be causative for Bardet-Biedl syndrome (Stoetzel et al. 2006. PubMed ID: 16582908, Table S1, reported as Y559fsX576). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-76740087-CG-C). Nonsense variants in BBS10 are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics	RCV000984154	SCV004217415	pathogenic	Bardet-Biedl syndrome 10	2023-10-16	criteria provided, single submitter	clinical testing
Invitae	RCV000586002	SCV004294233	pathogenic	Bardet-Biedl syndrome	2023-09-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BBS10 protein in which other variant(s) (p.Val707*) have been determined to be pathogenic (PMID: 20472660, 22773737, 25982971, 27486776). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 496471). This premature translational stop signal has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (PMID: 16582908, 20472660, 27788217, 28808579). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Tyr559*) in the BBS10 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 165 amino acid(s) of the BBS10 protein.
Counsyl	RCV000984154	SCV001132137	likely pathogenic	Bardet-Biedl syndrome 10	2015-05-04	no assertion criteria provided	clinical testing