Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000723707 | SCV000202224 | pathogenic | not provided | 2014-05-02 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000169072 | SCV000220239 | likely pathogenic | Bardet-Biedl syndrome 10 | 2014-04-09 | criteria provided, single submitter | literature only | |
Laboratory for Molecular Medicine, |
RCV000169072 | SCV000221174 | pathogenic | Bardet-Biedl syndrome 10 | 2014-08-04 | criteria provided, single submitter | clinical testing | The Asn364ThrfsX5 variant in BBS10 has been reported in 1 individual with Bardet Biedl syndrome in whom it was found to be in compound heterozygosity with another frameshift variant (Muller 2010). This variant was also not identified in large population studies. This frameshift variant is predicted to alter the protein’s amino acid sequence beginning at position 364 and lead to a premature termination codon 5 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathogenic (http://pcpgm.partners.org/LMM). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000152827 | SCV000699619 | pathogenic | Bardet-Biedl syndrome | 2016-06-09 | criteria provided, single submitter | clinical testing | Variant summary: The BBS10 c.1091delA (p.Asn364Thrfs) 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 6/121092 control chromosomes at a frequency of 0.0000495, which does not exceed the estimated maximal expected allele frequency of a pathogenic BBS10 variant (0.0013363). It was reported in several BBS patients in either homozygosity or compound heterozygosity with a disease causing variant indicating pathogenicity. Furthermore, truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1428delC, c.1677delC). Moreover, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Illumina Laboratory Services, |
RCV000169072 | SCV000914602 | pathogenic | Bardet-Biedl syndrome 10 | 2018-08-15 | criteria provided, single submitter | clinical testing | The BBS10 c.1091delA (p.Asn364ThrfsTer5) variant results in a frameshift, and is predicted to result in premature termination of the protein. Across four studies, the p.Asn364ThrfsTer5 variant has been identified in a total of four individuals with Bardet-Biedl syndrome (BBS) including in two in a homozygous state and in two in a compound heterozygous state with a second null variant (White et al. 2007; Muller et al. 2010; Chen et al. 2011; Pierrottet et al. 2014). One homozygous individual was also heterozygous for a missense variant in the BBS6 gene (Chen et al. 2011). Control data are unavailable for this variant, which is reported at a frequency of 0.001676 in the Ashkenazi Jewish population of the Genome Aggregation Database. Based on the evidence, the p.Asn364ThrfsTer5 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. |
Labcorp Genetics |
RCV000152827 | SCV000942345 | pathogenic | Bardet-Biedl syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn364Thrfs*5) in the BBS10 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 360 amino acid(s) of the BBS10 protein. This variant is present in population databases (rs727503818, gnomAD 0.2%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 20177705). ClinVar contains an entry for this variant (Variation ID: 166723). This variant disrupts a region of the BBS10 protein in which other variant(s) (p.Val707*) have been determined to be pathogenic (PMID: 20472660, 22773737, 25982971, 27486776). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV001004383 | SCV001163355 | pathogenic | Bardet-Biedl syndrome 1 | criteria provided, single submitter | clinical testing | ||
Victorian Clinical Genetics Services, |
RCV000169072 | SCV002768154 | pathogenic | Bardet-Biedl syndrome 10 | 2020-05-21 | criteria provided, single submitter | clinical testing | A heterozygous deletion variant was identified, NM_024685.4(BBS10):c.1091del in exon 2 of 2 of the BBS10 gene. This deletion is predicted to cause a frameshift from amino acid position 364 introducing a stop codon downstream; NP_078961.3(BBS10):p.(Asn364Thrfs*5), resulting in loss of normal protein function through truncation (half of the protein). The variant is present in the gnomAD population database at a global population frequency of 0.007% (19 heterozygotes, 0 homozygotes) with an Ashkenazi-Jewish sub-population frequency of 0.2%. It has been previously reported in patients with Bardet-Biedl syndrome (ClinVar; Manara, E. et al. (2019)). Other variants predicted to cause a truncated protein have been reported as pathogenic in individuals with Bardet-Biedl syndrome (ClinVar). Based on information available at the time of curation, this variant has been classified as PATHOGENIC. |
Fulgent Genetics, |
RCV000169072 | SCV002807212 | pathogenic | Bardet-Biedl syndrome 10 | 2024-06-07 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000169072 | SCV004217410 | pathogenic | Bardet-Biedl syndrome 10 | 2024-03-20 | criteria provided, single submitter | clinical testing | |
Laboratory of Medical Genetics |
RCV000152827 | SCV000839556 | pathogenic | Bardet-Biedl syndrome | 2018-09-15 | no assertion criteria provided | provider interpretation | |
Sharon lab, |
RCV000152827 | SCV001160906 | pathogenic | Bardet-Biedl syndrome | 2019-06-23 | no assertion criteria provided | research | |
Natera, |
RCV000169072 | SCV001462851 | pathogenic | Bardet-Biedl syndrome 10 | 2020-09-16 | no assertion criteria provided | clinical testing |