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

dbSNP: rs775950661

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000461059	SCV000544764	pathogenic	Bardet-Biedl syndrome	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val707*) in the BBS10 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 17 amino acid(s) of the BBS10 protein. This variant is present in population databases (rs775950661, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 20472660, 22773737, 25982971, 27486776). ClinVar contains an entry for this variant (Variation ID: 406221). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	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, Mass General Brigham 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, http://gnomad.broadinstitute.org; 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
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000665753	SCV001445876	pathogenic	Bardet-Biedl syndrome 10	2019-10-10	criteria provided, single submitter	clinical testing	This frameshifting variant in exon 2 of 2 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. 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 has been previously reported as a compound heterozygous or homozygous change in patients with Bardet-Biedl Syndrome 10 (PMID: 16582908, 25982971, 22773737, 27486776, 20472660). The ClinVar database contains an entry for this variant (Variation ID: 406221). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.006% (17/282614) and thus is presumed to be rare. Based on the available evidence, the c.2119_2120del (p.Val707Ter) variant is classified as Pathogenic.
GeneDx	RCV001731689	SCV001982879	pathogenic	not provided	2022-09-15	criteria provided, single submitter	clinical testing	Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 17 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); This variant is associated with the following publications: (PMID: 21157496, 31293383, 31963381, 16582908, 25982971, 30609409, 22773737, 27659767, 21209035, 27486776, 20472660, 34940782, 35112343)
Revvity Omics, Revvity	RCV000665753	SCV003824641	likely pathogenic	Bardet-Biedl syndrome 10	2023-06-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000665753	SCV004217416	pathogenic	Bardet-Biedl syndrome 10	2023-10-16	criteria provided, single submitter	clinical testing
Counsyl	RCV000665753	SCV000789921	pathogenic	Bardet-Biedl syndrome 10	2017-02-27	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000665753	SCV002091737	pathogenic	Bardet-Biedl syndrome 10	2020-01-18	no assertion criteria provided	clinical testing