Submissions for variant NM_031885.5(BBS2):c.2107C>T (p.Arg703Ter)

gnomAD frequency: 0.00001  dbSNP: rs567573386

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590291	SCV000699656	likely pathogenic	Bardet-Biedl syndrome	2017-06-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000622316	SCV000742127	likely pathogenic	Inborn genetic diseases	2017-01-24	criteria provided, single submitter	clinical testing
Invitae	RCV000590291	SCV000958736	pathogenic	Bardet-Biedl syndrome	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg703*) in the BBS2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acid(s) of the BBS2 protein. This variant is present in population databases (rs567573386, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with BBS2-related disease (PMID: 21344540, 25999675; Invitae). ClinVar contains an entry for this variant (Variation ID: 496478). For these reasons, this variant has been classified as Pathogenic.
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376258	SCV001573337	likely pathogenic	Retinitis pigmentosa 74	2021-04-08	criteria provided, single submitter	research	The BBS2 c.2107C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2. Based on this evidence we have classified this variant as Likely Pathogenic.
3billion	RCV001376258	SCV002521102	likely pathogenic	Retinitis pigmentosa 74	2022-05-22	criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000496478 / PMID: 21344540). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics	RCV000667111	SCV004213980	likely pathogenic	Bardet-Biedl syndrome 2	2024-03-20	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004530646	SCV004744331	likely pathogenic	BBS2-related disorder	2024-01-08	criteria provided, single submitter	clinical testing	The BBS2 c.2107C>T variant is predicted to result in premature protein termination (p.Arg703*). This variant has been reported in the homozygous state or with a second BBS2 variant in individuals with Bardet-Biedl syndrome (Deveault et al. 2011. PubMed ID: 21344540; Supplemental Table 1, Forsythe et al. 2016. PubMed ID: 27659767; Table S3, Fu et al. 2022. PubMed ID: 36307859) and reported in the homozygous state in an individual with retinitis pigmentosa (Xu et al. 2015. PubMed ID: 25999675). In addition, at PreventionGenetics, this variant has been seen in the homozygous or compound heterozygous states in individuals with features of Bardet-Biedl syndrome (Internal Data). This variant is reported in 0.027% of alleles in individuals of East Asian descent in a large population database. Nonsense variants in BBS2 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Counsyl	RCV000667111	SCV000791510	likely pathogenic	Bardet-Biedl syndrome 2	2017-05-15	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000667111	SCV001457430	likely pathogenic	Bardet-Biedl syndrome 2	2020-09-16	no assertion criteria provided	clinical testing