Submissions for variant NM_198428.3(BBS9):c.1280C>T (p.Ala427Val)

gnomAD frequency: 0.00599  dbSNP: rs138072724

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000174426	SCV000225724	benign	not specified	2014-10-21	criteria provided, single submitter	clinical testing
Invitae	RCV000204910	SCV000260907	benign	Bardet-Biedl syndrome	2024-01-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000174426	SCV000316936	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001095289	SCV000468794	likely benign	Bardet-Biedl syndrome 9	2018-01-12	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.
GeneDx	RCV000515021	SCV000516156	uncertain significance	not provided	2016-02-29	criteria provided, single submitter	clinical testing	The A427V variant in the BBS9 gene has been published previously as a rare sequence variant with a frequency of0.9% (Lim et al., 2014); this variant was identified in the homozygous state in 1/9033 control individuals. TheNHLBI Exome Sequencing Project reports A427V was observed in 0.79% (68/8600) alleles from individuals ofEuropean American ancestry, and was present in the homozygous state in one individual. The A427V variant is aconservative amino acid substitution, which is not likely to impact secondary protein structure as these residues sharesimilar properties. This substitution occurs at a position where amino acids with similar properties to Alanine aretolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant isdamaging to the protein structure/function. We interpret A427V as a variant of uncertain significance.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000515021	SCV000609814	likely benign	not provided	2017-02-22	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000174426	SCV002069884	benign	not specified	2021-06-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000515021	SCV004163892	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	BBS9: BP4, BS2