ClinVar Miner

Submissions for variant NM_024685.4(BBS10):c.271dup (p.Cys91fs) (rs549625604)

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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000168127 SCV000218785 pathogenic Bardet-Biedl syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BBS10 gene (p.Cys91Leufs*5). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 633 amino acids of the BBS10 protein. This variant is present in population databases (rs549625604, ExAC 0.1%). This variant is known to be a common cause of Bardet-Biedl syndrome (PMID: 16582908, 20805367, 27385962). ClinVar contains an entry for this variant (Variation ID: 1328). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000487323 SCV000331663 pathogenic not provided 2016-02-22 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000001391 SCV000381157 pathogenic Bardet-Biedl syndrome 10 2017-04-27 criteria provided, single submitter clinical testing The BBS10 c.271dupT (p.Cys91LeufsTer5) variant results in a frameshift and is predicted to result in premature termination of the protein. The p.Cys91LeufsTer5 is well-documented as a common founder mutation in several ethnic groups (Suspitsin et al. 2016). Stoetzel et al. (2006) sequenced 311 families with Bardet-Biedl syndrome (BBS) and found the p.Cys91LeufsTer5 variant in 18 patients in a homozygous state, 13 in a compound heterozygous state, and five in a heterozygous state, accounting for 46% of variants detected. BBS is known to follow a complex inheritance pattern; several individuals were found in this study who also carried a third variant in one of the other genes known to be associated with BBS. The p.Cys91LeufsTer5 variant has also been identified in a homozygous state in affected individuals from two families, one of Indian descent and one of Northern European descent; in a compound heterozygous state in a 20 year old woman with BBS; and in three fetal cases (Putoux et al. 2010; Lindstrand et al. 2014; Sathya Priya et al. 2015). Control data are unavailable for this variant which is reported at a frequency of 0.00121 in the European American population of the Exome Sequencing Project. Based on the evidence, the p.Cys91LeufsTer5 variant is classified as pathogenic for Bardet-Biedl syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Counsyl RCV000001391 SCV000485249 pathogenic Bardet-Biedl syndrome 10 2016-03-11 criteria provided, single submitter clinical testing
GeneDx RCV000487323 SCV000568844 pathogenic not provided 2018-08-09 criteria provided, single submitter clinical testing The c.271dupT pathogenic variant in the BBS10 gene has been reported many times in association with Bardet-Biedl syndrome (BBS)(Stoetzel et al., 2006). This variant is observed in the heterozygous state in 70/65,628 (0.1%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The duplication causes a frameshift starting with codon Cysteine 91, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Cys91LeufsX5. This pathogenic variant is predicted to cause loss of normal protein function through protein truncation, as the last 633 amino acids of the BBS10 protein are lost and replaced with 4 incorrect amino acids.
Genetic Services Laboratory, University of Chicago RCV000001391 SCV000593594 pathogenic Bardet-Biedl syndrome 10 2016-03-15 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000487323 SCV000612485 pathogenic not provided 2015-09-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000168127 SCV000699624 pathogenic Bardet-Biedl syndrome 2017-05-14 criteria provided, single submitter clinical testing Variant summary: The BBS10 c.271dupT (p.Cys91Leufs) 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. This variant was found in 81/119742 control chromosomes at a frequency of 0.0006765, which does not exceed the estimated maximal expected allele frequency of a pathogenic BBS10 variant (0.0013363). The variant of interest has been reported in multiple affected homozygous and compound heterozygous individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Ambry Genetics RCV000623309 SCV000740720 pathogenic Inborn genetic diseases 2014-08-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000709625 SCV000744062 pathogenic Bardet-Biedl syndrome 1 2016-01-27 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000709625 SCV000745512 pathogenic Bardet-Biedl syndrome 1 2017-05-31 criteria provided, single submitter clinical testing
MAGI'S LAB - Medical Genetics Laboratory,MAGI GROUP RCV000168127 SCV000897985 pathogenic Bardet-Biedl syndrome 2018-10-01 criteria provided, single submitter clinical testing
Department of Medical Genetics,Sanjay Gandhi Post Graduate Institute of Medical Sciences RCV000001391 SCV000902271 pathogenic Bardet-Biedl syndrome 10 criteria provided, single submitter clinical testing Sanger sequencing showed a homozygous sequence variant in BBS10 gene resulting in frameshift. It is predicted as pathogenic by MutationTaster. This variant is classified as pathogenic which shows strong evidence of pathogenicity according to ACMG guidelines (Richards et al., 2015). Parents were heterozygous for the same variation.
OMIM RCV000001391 SCV000021541 pathogenic Bardet-Biedl syndrome 10 2010-12-01 no assertion criteria provided literature only
OMIM RCV000144680 SCV000190013 pathogenic Bardet-biedl syndrome 6/10, digenic 2010-12-01 no assertion criteria provided literature only
Division of Human Genetics,Children's Hospital of Philadelphia RCV000709625 SCV000238414 pathogenic Bardet-Biedl syndrome 1 2014-07-17 no assertion criteria provided research This patient is a carrier of a heterozygous pathogenic variant in the BBS10 gene associated with for Bardet-Biedl syndrome 10. The BBS10 variant (c.271dup; p.Cys91Leufs*5) identified in this patient is a frameshift variant, reported to be one of the most common pathogenic variants for Bardet Biedl syndrome (Stoetzel et al. 2006, PMID: 16582908).
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504690 SCV000599084 pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
Laboratory of Medical Genetics, INSERM RCV000168127 SCV000839559 pathogenic Bardet-Biedl syndrome 2018-09-15 no assertion criteria provided provider interpretation
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000168127 SCV000926505 pathogenic Bardet-Biedl syndrome 2018-04-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000487323 SCV000926796 pathogenic not provided 2018-04-01 no assertion criteria provided research

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