ClinVar Miner

Submissions for variant NM_031885.4(BBS2):c.1894C>T (p.Arg632Cys) (rs200021475)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001094468 SCV000398049 uncertain significance Bardet-Biedl syndrome 2 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000326249 SCV001214898 uncertain significance Bardet-Biedl syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 632 of the BBS2 protein (p.Arg632Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs200021475, ExAC 0.03%). This variant has not been reported in the literature in individuals with BBS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 319852). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg632 amino acid residue in BBS2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25541840, 25133751,25412400). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Natera, Inc. RCV001094468 SCV001457499 uncertain significance Bardet-Biedl syndrome 2 2019-10-28 no assertion criteria provided clinical testing

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