Submissions for variant NM_031885.5(BBS2):c.1015C>T (p.Arg339Ter)

dbSNP: rs193922710

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029406	SCV000052054	pathogenic	Bardet-Biedl syndrome	2020-08-24	criteria provided, single submitter	clinical testing	Variant summary: BBS2 c.1015C>T (p.Arg339X) 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 was absent in 251404 control chromosomes (gnomAD). c.1015C>T has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (e.g. Shaheen_2016). 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 ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Counsyl	RCV000672755	SCV000797893	likely pathogenic	Bardet-Biedl syndrome 2	2018-02-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000029406	SCV001399563	pathogenic	Bardet-Biedl syndrome	2024-06-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg339*) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Bardet-Biedl syndrome (PMID: 27894351, 28387813). ClinVar contains an entry for this variant (Variation ID: 35754). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000672755	SCV004214022	pathogenic	Bardet-Biedl syndrome 2	2024-02-26	criteria provided, single submitter	clinical testing
GeneDx	RCV004719664	SCV005325989	pathogenic	not provided	2024-01-10	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32055034, 31630094, 31589614, 28387813, 33777945, 31725702, 27894351)
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV004798748	SCV005420464	pathogenic	Retinitis pigmentosa 74	2024-10-04	criteria provided, single submitter	research	PVS1,PM2,PM3
Fulgent Genetics, Fulgent Genetics	RCV005016297	SCV005644035	pathogenic	Bardet-Biedl syndrome 2; Retinitis pigmentosa 74	2024-03-23	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000672755	SCV002089283	pathogenic	Bardet-Biedl syndrome 2	2020-12-10	no assertion criteria provided	clinical testing