Submissions for variant NM_176824.3(BBS7):c.1505A>G (p.His502Arg)

gnomAD frequency: 0.00589  dbSNP: rs114718913

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001094938	SCV000447389	benign	Bardet-Biedl syndrome 7	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000435007	SCV000523495	uncertain significance	not provided	2016-02-21	criteria provided, single submitter	clinical testing	The H502R variant in the BBS7 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports H502R was observed in 87/4406 alleles (1.97%) from individuals of African American background, indicating it may be a rare variant in this population. The H502R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret H502R as a variant of uncertain significance.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000709647	SCV000743645	benign	Bardet-Biedl syndrome 1	2015-11-04	criteria provided, single submitter	clinical testing
Invitae	RCV000330267	SCV001001585	benign	Bardet-Biedl syndrome	2024-01-30	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001700075	SCV001921690	benign	not specified		no assertion criteria provided	clinical testing