rs1555202584
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_024685.4(BBS10):βc.1677delβ(p.Tyr559Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. Y559Y) has been classified as Likely benign.
Frequency
Consequence
NM_024685.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS10 | NM_024685.4 | c.1677del | p.Tyr559Ter | frameshift_variant | 2/2 | ENST00000650064.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS10 | ENST00000650064.2 | c.1677del | p.Tyr559Ter | frameshift_variant | 2/2 | NM_024685.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250830Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135594
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461502Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727058
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152128Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74310
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | MAGI'S LAB - Medical Genetics Laboratory, MAGI GROUP | Oct 01, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 24, 2023 | Variant summary: BBS10 c.1677delC (p.Tyr559X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in HGMD, ClinVar or our laboratory. The variant allele was found at a frequency of 4e-06 in 251022 control chromosomes. c.1677delC has been reported in the literature in individuals affected with Bardet-Biedl Syndrome. These data indicate that the variant may be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 10, 2023 | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 496471). This premature translational stop signal has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (PMID: 16582908, 20472660, 27788217, 28808579). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Tyr559*) in the BBS10 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 165 amino acid(s) of the BBS10 protein. - |
Bardet-Biedl syndrome 10 Pathogenic:2
Likely pathogenic, no assertion criteria provided | clinical testing | Counsyl | May 04, 2015 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 15, 2024 | - - |
BBS10-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 29, 2023 | The BBS10 c.1677delC variant is predicted to result in premature protein termination (p.Tyr559*). This variant has been reported to be causative for Bardet-Biedl syndrome (Stoetzel et al. 2006. PubMed ID: 16582908, Table S1, reported as Y559fsX576). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-76740087-CG-C). Nonsense variants in BBS10 are expected to be pathogenic. This variant is interpreted as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at