Submissions for variant NM_024685.4(BBS10):c.1631A>G (p.Asn544Ser)

gnomAD frequency: 0.00618  dbSNP: rs34737974

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000152824	SCV000202220	benign	not specified	2014-04-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084157	SCV000261859	benign	Bardet-Biedl syndrome	2025-01-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000152824	SCV000314383	likely benign	not specified		criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000438509	SCV000511659	likely benign	not provided	2016-09-15	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000152824	SCV000699621	benign	not specified	2021-09-03	criteria provided, single submitter	clinical testing	Variant summary: BBS10 c.1631A>G (p.Asn544Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function and Asn544 is not located in a known functional domain of the Bardet-Biedl syndrome 10 protein. A functional study is consistent with the finding that this variant is a functional polymorphism (Zaghloul_2010) as the mutant was unable to rescue the morphant phenotype in zebrafish. The variant allele was found at a frequency of 0.0076 in 251414 control chromosomes, predominantly at a frequency of 0.016 within the South Asian subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 13 fold of the estimated maximal expected allele frequency for a pathogenic variant in BBS10 causing Bardet-Biedl Syndrome phenotype (0.0012), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. Three ClinVar submitters (evaluation after 2014) cite the variant as benign (n=2) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as benign.
Illumina Laboratory Services, Illumina	RCV001112169	SCV001269805	benign	Bardet-Biedl syndrome 10	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.
Genetic Services Laboratory, University of Chicago	RCV000152824	SCV002068424	likely benign	not specified	2018-05-11	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000438509	SCV005216134	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001112169	SCV002091752	benign	Bardet-Biedl syndrome 10	2019-12-09	no assertion criteria provided	clinical testing