Submissions for variant NM_152618.3(BBS12):c.1859A>G (p.Gln620Arg)

gnomAD frequency: 0.00048  dbSNP: rs139278612

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000499698	SCV000593595	uncertain significance	not specified	2016-12-23	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000709681	SCV000744985	uncertain significance	Bardet-Biedl syndrome 1	2016-07-01	criteria provided, single submitter	clinical testing
Invitae	RCV000625333	SCV000759869	uncertain significance	Bardet-Biedl syndrome	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 620 of the BBS12 protein (p.Gln620Arg). This variant is present in population databases (rs139278612, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 22773737). ClinVar contains an entry for this variant (Variation ID: 434490). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BBS12 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Laboratory Services, Illumina	RCV001145003	SCV001305634	uncertain significance	Bardet-Biedl syndrome 12	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome-Nilou Lab	RCV001145003	SCV001781253	uncertain significance	Bardet-Biedl syndrome 12	2021-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001584212	SCV001810685	uncertain significance	not provided	2021-01-06	criteria provided, single submitter	clinical testing	Reported multiple times in the published literature, however association with disease is not well established (Redin et al., 2012; Griffith et al., 2018; Nozari et al., 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30507091, 28945142, 22773737)
PreventionGenetics, part of Exact Sciences	RCV003424055	SCV004116638	likely benign	BBS12-related condition	2023-12-06	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV001584212	SCV001920014	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001145003	SCV002084743	uncertain significance	Bardet-Biedl syndrome 12	2020-01-16	no assertion criteria provided	clinical testing