ClinVar Miner

Submissions for variant NM_031885.5(BBS2):c.1864C>T (p.Arg622Ter)

gnomAD frequency: 0.00001  dbSNP: rs201196733
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000424669 SCV000337475 pathogenic not provided 2015-12-08 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000424669 SCV000511629 likely pathogenic not provided 2017-01-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000531316 SCV000636526 pathogenic Bardet-Biedl syndrome 2024-07-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg622*) in the BBS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS2 are known to be pathogenic (PMID: 11285252, 20177705, 24608809, 26518167). This variant is present in population databases (rs201196733, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with Bardet-Biedl syndrome (PMID: 21344540, 26078953). ClinVar contains an entry for this variant (Variation ID: 284737). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000335732 SCV000916672 pathogenic Bardet-Biedl syndrome 2 2018-03-02 criteria provided, single submitter clinical testing Variant summary: BBS2 c.1864C>T (p.Arg622X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A truncation downstream of this position has been classified as likely pathogenic by our laboratory, c.2107C>T (p.Arg703X). The variant has been observed with an allele frequency of 2.8e-05 in 246196 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BBS2 causing Bardet-Biedl Syndrome (2.8e-05 vs. 8.5e-04), allowing no conclusion about variant significance. The variant, c.1864C>T, has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (Bee 2015, Deveault 2011). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) have classified the variant as "likely pathogenic/pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV000335732 SCV002557552 pathogenic Bardet-Biedl syndrome 2 2022-02-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Bardet-Biedl syndrome 2 (MIM#615981) and retinitis pigmentosa 74 (MIM#616562). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 7 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (Decipher; PMID: 31283077). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been classified as likely pathogenic or pathogenic by clinical diagnostic laboratories and has been reported as compound heterozygous in individuals with Bardet-Biedl syndrome 2 (ClinVar; PMIDs: 21344540, 26078953). This variant is also compound heterozygous in one individual with chronic kidney disease without a specific diagnosis and heterozygous in an individual with inherited retinal disease (PMIDs: 33226606, 31429209). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Fulgent Genetics, Fulgent Genetics RCV002502120 SCV002788710 pathogenic Bardet-Biedl syndrome 2; Retinitis pigmentosa 74 2024-05-09 criteria provided, single submitter clinical testing
Baylor Genetics RCV000335732 SCV004214002 pathogenic Bardet-Biedl syndrome 2 2023-09-20 criteria provided, single submitter clinical testing
Counsyl RCV000335732 SCV000486377 likely pathogenic Bardet-Biedl syndrome 2 2016-11-02 no assertion criteria provided clinical testing

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