ClinVar Miner

Submissions for variant NM_024685.4(BBS10):c.2119_2120del (p.Thr706_Val707insTer) (rs775950661)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000461059 SCV000544764 pathogenic Bardet-Biedl syndrome 2019-12-26 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 2 of the BBS10 mRNA (c.2119_2120delGT), causing a frameshift at codon 707. This creates a premature translational stop signal in the last exon of the BBS10 mRNA (p.Val707*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 17 amino acids of the BBS10 protein. This variant is present in population databases (rs775950661, ExAC 0.01%). This variant occurs in the homozygous state or with a pathogenic or second rare variant in BBS10 in several individuals affected with Bardet-Biedl syndrome (PMID: 25982971, 22773737, 27486776, 20472660). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000461059 SCV000699623 pathogenic Bardet-Biedl syndrome 2017-08-22 criteria provided, single submitter clinical testing Variant summary: The BBS10 c.2119_2120delGT (p.Val707Terfs) variant results in a premature termination codon, predicted to cause a truncated or absent BBS10 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 8/121352 control chromosomes at a frequency of 0.0000659, which does not exceed the estimated maximal expected allele frequency of a pathogenic BBS10 variant (0.0013363). This variant has been reported in multiple BBS patients. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000461059 SCV000967598 likely pathogenic Bardet-Biedl syndrome 2018-02-07 criteria provided, single submitter clinical testing The p.Val707X (NM_024685.3 c.2119_2120delGT) variant in BBS10 has been previousl y reported in at least one compound heterozygous and one homozygous individual w ith Bardet-Biedl syndrome (BBS) (Stoetzel 2006, Scheidecker 2015, Lindstrand 201 6). This variant has also been reported in ClinVar (Variation ID#406221) as path ogenic. It has been identified in (15/126,508) of European chromosomes by the Ge nome Aggregation Database (gnomAD,; dbSNP rs775 950661). Although this variant has been seen in the general population, its freq uency is low enough to be consistent with a recessive carrier frequency. This no nsense variant leads to a premature termination codon at position 707, which is predicted to lead to a truncated or absent protein. Biallelic loss of function o f the BBS10 gene has been associated with Bardet-Biedl syndrome (BBS). In summar y, although additional studies are required to fully establish its clinical sign ificance, the p.Val707X variant is likely pathogenic for Bardet-Biedl syndrome ( BBS) in an autosomal recessive manner based on a predicted truncating effect and its biallelic occurrence in individuals with this disease.
Blueprint Genetics RCV001074511 SCV001240098 pathogenic Retinal dystrophy 2017-12-09 criteria provided, single submitter clinical testing
Counsyl RCV000665753 SCV000789921 pathogenic Bardet-Biedl syndrome 10 2017-02-27 no assertion criteria provided clinical testing

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