Submissions for variant NM_031885.5(BBS2):c.1511C>T (p.Ala504Val)

gnomAD frequency: 0.02076  dbSNP: rs16957538

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000203892	SCV000260909	benign	Bardet-Biedl syndrome	2025-02-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000245072	SCV000314810	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094290	SCV000398055	benign	Bardet-Biedl syndrome 2	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000086984	SCV000699653	likely benign	not provided	2016-01-11	criteria provided, single submitter	clinical testing	Variant summary: This c.1511C>T variant affects a non-conserved nucleotide, resulting in amino acid change from a small size and hydrophobic residue (A) to medium size and hydrophobic residue (V). 3/4 in-silico tools predict this variant to be benign; however, functional studies have not been carried out to confirm these predictions. This variant is found in 741/121412 control chromosomes (including 19 homozygotes) at a frequency of 0.0061032, which is about 7 times greater than the maximal expected frequency of a pathogenic BBS2 allele (0.0008452), suggesting this variant is benign. It was found to co-occur in patients with 2 pathogenic variants in the BBS1 gene, and did not co-segregate in a manner consistent with BBS (Mykytyn_2003). This finding is consistent with its co-occurrence with two confirmed pathogenic BBS1 variants (p.M390R and c.607delA) in a subject tested in our laboratory. This variant has also been reported in patients with thrombosis mechanistic phenotype; however, it was not significantly associated with increased odds ratio (Mosley_2013). There are no functional studies reported for this variant. A digenic and tri-allelic locus interactions have been reported in patients with BBS. This variant's role in such interaction and whether this variant plays a modifier role for another pathogenic variant has not been fully explored. The variant has not been reported in reputable databases. Based on currently available information this variant has been classified as Likely Benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000709639	SCV000743749	benign	Bardet-Biedl syndrome 1	2014-12-23	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000709639	SCV000745153	benign	Bardet-Biedl syndrome 1	2015-09-21	criteria provided, single submitter	clinical testing
GeneDx	RCV000086984	SCV001903588	benign	not provided	2021-05-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27058611)
Breakthrough Genomics, Breakthrough Genomics	RCV000086984	SCV005216482	likely benign	not provided		criteria provided, single submitter	not provided
NEI Ophthalmic Genomics Laboratory, National Institutes of Health	RCV000086984	SCV000119237	not provided	not provided		no assertion provided	not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000086984	SCV001798876	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001094290	SCV002089273	benign	Bardet-Biedl syndrome 2	2019-11-12	no assertion criteria provided	clinical testing