ClinVar Miner

Submissions for variant NM_031885.5(BBS2):c.98C>A (p.Ala33Asp)

gnomAD frequency: 0.00001  dbSNP: rs797045155
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001380380 SCV001578425 pathogenic Bardet-Biedl syndrome 2023-07-29 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 33 of the BBS2 protein (p.Ala33Asp). This variant is present in population databases (rs797045155, gnomAD 0.003%). This missense change has been observed in individual(s) with Bardet-Biedl syndrome and/or nonsyndromic retinitis pigmentosa (PMID: 25541840; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 209042). 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 BBS2 protein function. For these reasons, this variant has been classified as Pathogenic.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000675055 SCV001976998 likely pathogenic Bardet-Biedl syndrome 2 2021-10-01 criteria provided, single submitter clinical testing PM2, PP3, PP4, PP5
Myriad Genetics, Inc. RCV000675055 SCV002060274 uncertain significance Bardet-Biedl syndrome 2 2021-11-15 criteria provided, single submitter clinical testing NM_031885.3(BBS2):c.98C>A(A33D) is a missense variant classified as a variant of uncertain significance in the context of Bardet-Biedl syndrome, BBS2-related. A33D has not been observed in cases with relevant disease. Functional assessments of this variant are not available in the literature. A33D has been observed in population frequency databases (gnomAD: AMR 0.003%). In summary, there is insufficient evidence to classify NM_031885.3(BBS2):c.98C>A(A33D) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
PreventionGenetics, part of Exact Sciences RCV004539761 SCV004764088 uncertain significance BBS2-related disorder 2024-02-01 criteria provided, single submitter clinical testing The BBS2 c.98C>A variant is predicted to result in the amino acid substitution p.Ala33Asp. This variant was reported in the compound heterozygous state in three siblings who presented with retinitis pigmentosa (Shevach et al. 2015. PubMed ID: 25541840). This variant was also described in the apparently homozygous state in at least two other individuals with retinitis pigmentosa or suspected Bardet-Biedl syndrome; however, additional clinical and familial details were not provided (Sharon et al. 2019. PubMed ID: 31456290, supplementary data; Marinakis et al. 2021. PubMed ID: 34008892). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
OMIM RCV000190987 SCV000245874 pathogenic Retinitis pigmentosa 74 2015-03-01 no assertion criteria provided literature only
Sharon lab, Hadassah-Hebrew University Medical Center RCV001002878 SCV001160911 likely pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research

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