ClinVar Miner

Submissions for variant NM_152618.3(BBS12):c.1092del (p.Glu365fs) (rs770218590)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000675164 SCV000447409 uncertain significance Bardet-Biedl syndrome 12 2017-04-28 criteria provided, single submitter clinical testing The BBS12 c.1092delA (p.Glu365ArgfsTer18) variant results in a frameshift and is predicted to cause a premature termination of the protein. This variant has been reported in a compound heterozygous state in one individual with Bardet-Biedl syndrome (Stoetzel et al. 2007). Frequency information is not available from the 1000 Genomes Project, the Exome Sequencing Project or the Exome Aggregation Consortium, even though the variant lies in a region of good sequence coverage, suggesting that it is a rare variant. Due to the potential impact of frameshift variants and the limited information available, the p.Glu365ArgfsTer18 variant is classified as a variant of unknown significance but suspicious for pathogenicity for Bardet-Biedl syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Blueprint Genetics RCV001073939 SCV001239504 likely pathogenic Retinal dystrophy 2018-07-16 criteria provided, single submitter clinical testing
Invitae RCV001210623 SCV001382119 pathogenic Bardet-Biedl syndrome 2019-08-21 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BBS12 gene (p.Glu365Argfs*18). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 346 amino acids of the BBS12 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in combination with another BBS12 variant in individuals affected with Bardet-Biedl syndrome (PMID: 17160889, 27659767). ClinVar contains an entry for this variant (Variation ID: 347497). This variant disrupts the C-terminus of the BBS12 protein. Other variant(s) that disrupt this region (p.Arg675*) have been determined to be pathogenic (PMID: 20827784, 21642631). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000675164 SCV000800781 pathogenic Bardet-Biedl syndrome 12 2017-08-08 no assertion criteria provided clinical testing

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