Submissions for variant NM_152618.3(BBS12):c.1115_1116del (p.Gly371_Phe372insTer)

dbSNP: rs587777803

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000419202	SCV000510592	pathogenic	not provided	2017-01-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000419202	SCV000609146	likely pathogenic	not provided	2017-03-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000735936	SCV000951078	pathogenic	Bardet-Biedl syndrome	2024-01-12	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe372*) in the BBS12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 339 amino acid(s) of the BBS12 protein. This variant is present in population databases (rs753781824, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with Bardet-Biedl syndrome (PMID: 17160889, 20827784, 24611592). This variant is also known as 1114delTT. ClinVar contains an entry for this variant (Variation ID: 1151). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001073576	SCV001239127	pathogenic	Retinal dystrophy	2019-06-29	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000001210	SCV001752511	pathogenic	Bardet-Biedl syndrome 12	2022-04-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000419202	SCV001793754	pathogenic	not provided	2023-12-19	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation, as the last 339 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; This variant is associated with the following publications: (PMID: 24611592, 32531858, 17160889, 20142850, 20876674, 21344540, 28157192, 30614526, 31047384, 31589614, 34426522, 35886001, 35835773, 31964843, 35368817, 20827784)
Revvity Omics, Revvity	RCV000001210	SCV002024450	pathogenic	Bardet-Biedl syndrome 12	2021-02-24	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000001210	SCV004211654	pathogenic	Bardet-Biedl syndrome 12	2024-03-13	criteria provided, single submitter	clinical testing
OMIM	RCV000001210	SCV000021360	pathogenic	Bardet-Biedl syndrome 12	2007-01-01	no assertion criteria provided	literature only
Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University	RCV000735936	SCV000839574	pathogenic	Bardet-Biedl syndrome	2018-09-15	no assertion criteria provided	provider interpretation
Natera, Inc.	RCV000001210	SCV001462014	pathogenic	Bardet-Biedl syndrome 12	2020-09-16	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003398410	SCV004104085	pathogenic	BBS12-related disorder	2024-08-20	no assertion criteria provided	clinical testing	The BBS12 c.1115_1116delTT variant is predicted to result in premature protein termination (p.Phe372*). This variant, also defined as c.1114_1115del (p.Phe372fs*373), has been reported in the homozygous or compound heterozgyous states in individuals with Bardet-Biedl syndrome or retinitis pigmentosa (see, for example, Stoetzel et al. 2007. PubMed ID: 17160889; Hariri et al. 2018. PubMed ID: 31047384). This variant is reported in 0.017% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in BBS12 are expected to be pathogenic. This variant is interpreted as pathogenic.