Submissions for variant NM_024685.4(BBS10):c.424G>A (p.Asp142Asn)

gnomAD frequency: 0.00738  dbSNP: rs142863601

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000152829	SCV000052051	benign	not specified	2017-06-23	criteria provided, single submitter	clinical testing	Variant summary: The c.424G>A (p.Asp142Asn) in BBS10 gene is a missense change that involves a mildly conserved nucleotide and 3/4 in silico tools predict deleterious outcome. In In vivo experiments D142N was able to rescue the morphant phenotype similarly to the WT and was classified as "Benign" change (Zaghloul, 2010) (BS3). The variant was found in the large and broad cohorts of ExAC project at an allele frequency of 0.0083 (1005/120074 chrs tested), predominantly in individuals of European ancestry (0.0133; 878/65994, including 7/9 homozygotes). This observed frequencies exceed the maximal expected allele frequency of a disease causing BBS10 allele (0.0013) (BS1). The variant was identified in compound heterozygosity with BBS10 c.92C>T (p.P31L) in a BBS patient with a limited clinical information. It is not clear, whether c.424G>A was contributing to the clinical presentation of the patient or whether the real causal mutation may have been missed (Feuillan, 2011). In addition, the possibility of the variant being a modifier or a partner in a “triallelic inheritance” cannot be completely ruled out. The variant was identified in Joubert Syndrome (JS) patient who carried two causative mutations in TME231 and was proposed to be a potential modifier. Lastly, the variant of interest has been reported as “Likely Benign/Benign” by reputable databases/clinical laboratories (BP6). Taking together, by applying ACMG guidelines the variant was classified as Benign.
Eurofins Ntd Llc (ga)	RCV000152829	SCV000202225	benign	not specified	2014-01-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079951	SCV000218829	benign	Bardet-Biedl syndrome	2025-02-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000152829	SCV000246779	benign	not specified	2018-02-21	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224320	SCV000280907	likely benign	not provided	2016-04-22	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
PreventionGenetics, part of Exact Sciences	RCV000152829	SCV000314386	likely benign	not specified		criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000709626	SCV000744061	benign	Bardet-Biedl syndrome 1	2014-12-11	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000709626	SCV000745981	benign	Bardet-Biedl syndrome 1	2017-04-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001111799	SCV001269398	likely benign	Bardet-Biedl syndrome 10	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Fulgent Genetics, Fulgent Genetics	RCV001111799	SCV002807325	likely benign	Bardet-Biedl syndrome 10	2021-07-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000224320	SCV004135492	benign	not provided	2024-10-01	criteria provided, single submitter	clinical testing	BBS10: BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000224320	SCV005216136	likely benign	not provided		criteria provided, single submitter	not provided
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000152829	SCV001959736	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001111799	SCV002091789	likely benign	Bardet-Biedl syndrome 10	2019-11-14	no assertion criteria provided	clinical testing