ClinVar Miner

Submissions for variant NM_031885.4(BBS2):c.72C>G (p.Tyr24Ter) (rs121908175)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000589350 SCV000699658 pathogenic Bardet-Biedl syndrome 2017-08-10 criteria provided, single submitter clinical testing Variant summary: The BBS2 c.72C>G (p.Tyr24X) variant results in a premature termination codon, predicted to cause a truncated or absent BBS2 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 7/116822 control chromosomes at a frequency of 0.0000599, which does not exceed the estimated maximal expected allele frequency of a pathogenic BBS2 variant (0.0008452). This variant has been reported in multiple BBS patients in homozygous or compound heterozygous state. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000762970 SCV000893411 pathogenic Bardet-Biedl syndrome 2; Retinitis pigmentosa 74 2018-10-31 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group,Broad Institute RCV000412476 SCV000924501 likely pathogenic Bardet-Biedl syndrome 2 2018-06-15 criteria provided, single submitter research The heterozygous p.Tyr24Ter variant was identified by our study in the compound heterozygous state, with a VUS, in one individual with Bardet-Biedl syndrome. This variant has been identified in <0.01% (12/125738) of European (Non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs121908175). Loss of function of the BBS2 gene is an established disease mechanism in autosomal recessive Bardet-Biedl syndrome 2, and this is a loss of function variant. In summary, although additional studies are required to fully establish its pathogenicity, this variant is likely pathogenic.
Invitae RCV000589350 SCV000940175 pathogenic Bardet-Biedl syndrome 2019-12-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr24*) in the BBS2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs121908175, ExAC 0.01%). This variant has been observed to be homozygous or in combination with another BBS2 variant in several individuals affected with Bardet-Biedl syndrome (PMID: 11567139, 21344540). ClinVar contains an entry for this variant (Variation ID: 4570). Loss-of-function variants in BBS2 are known to be pathogenic (PMID: 11285252). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074960 SCV001240567 pathogenic Retinal dystrophy 2017-09-18 criteria provided, single submitter clinical testing
OMIM RCV000004832 SCV000025008 pathogenic Bardet-biedl syndrome 2/6, digenic 2001-09-21 no assertion criteria provided literature only
Counsyl RCV000412476 SCV000486607 pathogenic Bardet-Biedl syndrome 2 2016-11-03 no assertion criteria provided clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787792 SCV000926802 pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research

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