Submissions for variant NM_031885.5(BBS2):c.563del (p.Ile188fs)

gnomAD frequency: 0.00001  dbSNP: rs1367927635

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000667813	SCV000792318	likely pathogenic	Bardet-Biedl syndrome 2	2017-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV001224369	SCV001396559	pathogenic	Bardet-Biedl syndrome	2023-11-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile188Thrfs*13) in the BBS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS2 are known to be pathogenic (PMID: 11285252, 20177705, 24608809, 26518167). This variant is present in population databases (no rsID available, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with Bardet-Biedl syndrome and retinitis pigmentosa (PMID: 24608809, 31960602). ClinVar contains an entry for this variant (Variation ID: 552531). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001224369	SCV001774528	pathogenic	Bardet-Biedl syndrome	2021-07-11	criteria provided, single submitter	clinical testing	Variant summary: BBS2 c.563delT (p.Ile188ThrfsX13) 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 8e-06 in 251312 control chromosomes. c.563delT has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (example, Xing_2014, Dan_2020, Meng_2021). 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. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV002477490	SCV002784318	pathogenic	Bardet-Biedl syndrome 2; Retinitis pigmentosa 74	2021-08-17	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000667813	SCV004213985	pathogenic	Bardet-Biedl syndrome 2	2024-03-25	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000667813	SCV002089301	pathogenic	Bardet-Biedl syndrome 2	2020-02-01	no assertion criteria provided	clinical testing
Department of Pediatrics, National Cheng-Kung University Hospital	RCV000667813	SCV004042839	pathogenic	Bardet-Biedl syndrome 2		no assertion criteria provided	clinical testing