ClinVar Miner

Submissions for variant NM_031885.5(BBS2):c.1673C>T (p.Thr558Ile)

gnomAD frequency: 0.00001  dbSNP: rs370581600
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001348771 SCV001543086 uncertain significance Bardet-Biedl syndrome 2022-05-21 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 558 of the BBS2 protein (p.Thr558Ile). This variant is present in population databases (rs370581600, gnomAD 0.0009%). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 12016587). This missense change has been observed to be homozygous or hemizygous in an individual who did not have the expected clinical features for that genetic result (PMID: 12016587). ClinVar contains an entry for this variant (Variation ID: 1044521). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BBS2 function (PMID: 20498079). 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.
Dept Of Ophthalmology, Nagoya University RCV003888053 SCV004705054 likely pathogenic Retinal dystrophy 2023-10-01 criteria provided, single submitter research
Natera, Inc. RCV001831145 SCV002089266 uncertain significance Bardet-Biedl syndrome 2 2020-03-02 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004733265 SCV005342456 uncertain significance BBS2-related disorder 2024-04-06 no assertion criteria provided clinical testing The BBS2 c.1673C>T variant is predicted to result in the amino acid substitution p.Thr558Ile. This variant was reported in the homozygous state in an individual with Bardet-Biedl syndrome, although it was also found in the homozygous state in unaffected family members; the affected individual was also homozygous for a missense variant (p.Ala364Glu) in the BBS4 gene (Family PB043 in Figure 3, Katsanis et al. 2002. PubMed ID: 12016587). Functional studies suggested the p.Thr558Ile substitution may exhibit a dominant negative effect (Zaghloul et al. 2010. PubMed ID: 20498079). This variant has not been reported in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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