Submissions for variant NM_152618.3(BBS12):c.116T>C (p.Ile39Thr)

gnomAD frequency: 0.00577  dbSNP: rs138036823

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000082656	SCV000114698	benign	not specified	2013-11-20	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000082656	SCV000246780	benign	not specified	2018-09-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000082656	SCV000316216	benign	not specified		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080843	SCV000558135	benign	Bardet-Biedl syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000513736	SCV000610341	likely benign	not provided	2017-05-09	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000709646	SCV000743646	benign	Bardet-Biedl syndrome 1	2014-12-22	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000626298	SCV000746959	uncertain significance	Bardet-Biedl syndrome 12	2017-12-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000626298	SCV001305522	likely benign	Bardet-Biedl syndrome 12	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genome-Nilou Lab	RCV000626298	SCV001653381	uncertain significance	Bardet-Biedl syndrome 12	2021-05-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000082656	SCV002104097	likely benign	not specified	2022-02-22	criteria provided, single submitter	clinical testing	Variant summary: BBS12 c.116T>C (p.Ile39Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0063 in 251186 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 8 fold of the estimated maximal expected allele frequency for a pathogenic variant in BBS12 causing Bardet-Biedl Syndrome phenotype (0.00076), strongly suggesting that the variant is benign. c.116T>C has been reported in the literature in individuals affected with Bardet-Biedl Syndrome. These report(s) do not provide unequivocal conclusions about association of the variant with Bardet-Biedl Syndrome. At-least one co-occurrence with other pathogenic variant(s) have been reported (BBS12 c.814C>T, p.Arg272*), providing supporting evidence for a benign role (example, Manara_2019). One publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Zaghoul_2010). Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000513736	SCV004148816	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	BBS12: BS2
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000709646	SCV000745765	likely benign	Bardet-Biedl syndrome 1	2017-04-19	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000082656	SCV001924835	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000626298	SCV002082474	benign	Bardet-Biedl syndrome 12	2019-11-13	no assertion criteria provided	clinical testing