rs764164384
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_031885.5(BBS2):c.814C>T(p.Arg272Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R272R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_031885.5 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS2 | NM_031885.5 | c.814C>T | p.Arg272Ter | stop_gained | 8/17 | ENST00000245157.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS2 | ENST00000245157.11 | c.814C>T | p.Arg272Ter | stop_gained | 8/17 | 1 | NM_031885.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251294Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135844
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727234
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 2 Pathogenic:4
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 07, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 30, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 08, 2017 | Variant summary: The BBS2 c.814C>T (p.Arg272X) 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. A truncation downstream of this position, c.823C>T (p.Arg275X) has been classified as pathogenic by our laboratory. This variant was found in 3/246118 control chromosomes at a frequency of 0.0000122, which does not exceed the estimated maximal expected allele frequency of a pathogenic BBS2 variant (0.0008452). Multiple publications have cited the variant in homozygous affected individuals. The variant of interest has not, to our knowledge, been cited and classified by clinical diagnostic laboratories. Taken together, this variant is classified as pathogenic. - |
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 03, 2022 | Nonsense variant predicted to result in protein truncation or nonsense-mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 28559085, 25780760, 31196119, 11285252) - |
Pathogenic, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Bardet-Biedl syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | research | SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 26, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 552219). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 11285252, 28559085). This variant is present in population databases (rs764164384, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg272*) in the BBS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS2 are known to be pathogenic (PMID: 11285252, 20177705, 24608809, 26518167). - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Bardet-Biedl syndrome 2;C4225281:Retinitis pigmentosa 74 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 03, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at