ClinVar Miner

Submissions for variant NM_176824.3(BBS7):c.968A>G (p.His323Arg)

gnomAD frequency: 0.00010  dbSNP: rs119466001
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001091375 SCV001247389 pathogenic not provided 2018-04-01 criteria provided, single submitter clinical testing
Invitae RCV001240994 SCV001413983 pathogenic Bardet-Biedl syndrome 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 323 of the BBS7 protein (p.His323Arg). This variant is present in population databases (rs119466001, gnomAD 0.008%). This missense change has been observed in individuals with Bardet-Biedl syndrome (PMID: 12567324, 32531858). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 3015). 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 not expected to disrupt BBS7 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects BBS7 function (PMID: 20498079, 22302990). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001091375 SCV001446875 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
GeneDx RCV001091375 SCV001791546 likely pathogenic not provided 2020-10-15 criteria provided, single submitter clinical testing Published functional studies demonstrate H323R impacts the rate of BBS7 nuclear export through a dominant negative mechanism (Zaghloul et al., 2010; Gascue et al., 2012); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 12567324, 20498079, 31589614, 22302990)
Baylor Genetics RCV000003151 SCV004214135 likely pathogenic Bardet-Biedl syndrome 7 2023-09-30 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003964791 SCV004777565 pathogenic BBS7-related condition 2024-01-24 criteria provided, single submitter clinical testing The BBS7 c.968A>G variant is predicted to result in the amino acid substitution p.His323Arg. This variant has been found in the homozygous state in three individuals with Bardet-Biedl syndrome from two families (Badano et al. 2003. PubMed ID: 12567324). Functional studies indicate this variant disrupts BBS7 function (Zaghloul et al. 2010. PubMed ID: 20498079; Gascue et al. 2012. PubMed ID: 22302990). This variant is reported in 0.0080% of alleles in individuals of African descent in gnomAD. This variant is interpreted as pathogenic.
OMIM RCV000003151 SCV000023309 pathogenic Bardet-Biedl syndrome 7 2003-03-01 no assertion criteria provided literature only

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