ClinVar Genomic variation as it relates to human health
NM_031885.5(BBS2):c.175C>T (p.Gln59Ter)
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_031885.5(BBS2):c.175C>T (p.Gln59Ter)
Variation ID: 4571 Accession: VCV000004571.44
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16q13 16: 56514623 (GRCh38) [ NCBI UCSC ] 16: 56548535 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 28, 2017 Jun 29, 2025 Dec 13, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_031885.5:c.175C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_114091.4:p.Gln59Ter nonsense NM_001377456.1:c.175C>T NP_001364385.1:p.Gln59Ter nonsense NR_165293.1:n.337C>T non-coding transcript variant NR_165294.1:n.337C>T non-coding transcript variant NR_165295.1:n.337C>T non-coding transcript variant NR_165296.1:n.337C>T non-coding transcript variant NR_165297.1:n.337C>T non-coding transcript variant NC_000016.10:g.56514623G>A NC_000016.9:g.56548535G>A NG_009312.2:g.10402C>T - Protein change
- Q59*
- Other names
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- Canonical SPDI
- NC_000016.10:56514622:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BBS2 | - | - |
GRCh38 GRCh37 |
1215 | 1265 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Mar 12, 2024 | RCV000004833.11 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 13, 2024 | RCV000587533.12 | |
Pathogenic (1) |
criteria provided, single submitter
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May 9, 2022 | RCV002490314.1 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Apr 22, 2023 | RCV003441704.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jan 31, 2019)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699654.2
First in ClinVar: Mar 17, 2018 Last updated: Nov 08, 2019 |
Comment:
Variant summary: BBS2 c.175C>T (p.Gln59X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BBS2 c.175C>T (p.Gln59X) 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 by our laboratory (eg. c.814C>T (p.Arg272X), c.823C>T (p.Arg275X), and c.1864C>T (p.Arg622X)). The variant allele was found at a frequency of 2.4e-05 in 246604 control chromosomes (gnomAD and publications). c.175C>T has been reported in the literature in individuals affected with features of Bardet-Biedl Syndrome (Katsanis_2001, Fitzgerald_2015). Katsanis_2001 proposed that this syndrome may not be a single-gene recessive disease but a complex trait requiring three mutant alleles to manifest the phenotype because an affected patient from one family carried triallelic variants BBS2 Q59X and Y24X in compound heterozygosity and BBS6 Q147X, while a sibling with the same biallelic variants in BBS2 without the BBS6 variant and father with BBS2 Q59X and BBS6 Q147X were healthy. Another publication, Abu-Safieh_2012, using a cohort of 29 BBS families was not able to support this triallelic model, arguing in favor of straightforward autosomal recessive BBS in most cases. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(May 09, 2022)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 2
Retinitis pigmentosa 74
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002779927.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Aug 09, 2022)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 2
Affected status: yes
Allele origin:
inherited
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Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University
Accession: SCV002559829.2
First in ClinVar: Feb 13, 2023 Last updated: Aug 13, 2023 |
Number of individuals with the variant: 1
Zygosity: Homozygote
Secondary finding: no
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Likely pathogenic
(Apr 22, 2023)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV004170717.1
First in ClinVar: Nov 25, 2023 Last updated: Nov 25, 2023 |
Comment:
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 … (more)
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: 27659767, 28911095, 26147798, 11567139, 21962508, 25533962, 21052717) (less)
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Pathogenic
(Mar 12, 2024)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 2
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004214019.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Dec 13, 2024)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000955325.7
First in ClinVar: Aug 14, 2019 Last updated: Feb 25, 2025 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln59*) in the BBS2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln59*) 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). This variant is present in population databases (rs121908176, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 11567139, 27659767). ClinVar contains an entry for this variant (Variation ID: 4571). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 21, 2001)
N
Not contributing to aggregate classification
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no assertion criteria provided
Method: literature only
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BARDET-BIEDL SYNDROME 2
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000025009.3
First in ClinVar: Apr 04, 2013 Last updated: Apr 28, 2017 |
Comment on evidence:
In a BBS2 (615981) patient, Katsanis et al. (2001) identified compound heterozygosity for a glutamine-to-termination substitution at codon 59 in the BBS2 gene. This mutation … (more)
In a BBS2 (615981) patient, Katsanis et al. (2001) identified compound heterozygosity for a glutamine-to-termination substitution at codon 59 in the BBS2 gene. This mutation was found with the Y24X mutation (606151.0003) and also the gln147-to-ter mutation in MKKS (604896.0012). (less)
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Pathogenic
(Sep 16, 2020)
N
Not contributing to aggregate classification
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no assertion criteria provided
Method: clinical testing
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Bardet-Biedl syndrome type 2
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001458477.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Pathogenic
(Aug 25, 2017)
N
Not contributing to aggregate classification
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no assertion criteria provided
Method: clinical testing
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Bardet-Biedl syndrome 2
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000793615.3
First in ClinVar: Apr 28, 2017 Last updated: Jun 29, 2025 |
Comment:
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Risk Factors for Severe Renal Disease in Bardet-Biedl Syndrome. | Forsythe E | Journal of the American Society of Nephrology : JASN | 2017 | PMID: 27659767 |
Targeted multi-gene panel testing for the diagnosis of Bardet Biedl syndrome: Identification of nine novel mutations across BBS1, BBS2, BBS4, BBS7, BBS9, BBS10 genes. | Ece Solmaz A | European journal of medical genetics | 2015 | PMID: 26518167 |
Large-scale discovery of novel genetic causes of developmental disorders. | Deciphering Developmental Disorders Study | Nature | 2015 | PMID: 25533962 |
Comprehensive molecular diagnosis of Bardet-Biedl syndrome by high-throughput targeted exome sequencing. | Xing DJ | PloS one | 2014 | PMID: 24608809 |
Arrayed primer extension technology simplifies mutation detection in Bardet-Biedl and Alström syndrome. | Pereiro I | European journal of human genetics : EJHG | 2011 | PMID: 21157496 |
Mutation analysis in Bardet-Biedl syndrome by DNA pooling and massively parallel resequencing in 105 individuals. | Janssen S | Human genetics | 2011 | PMID: 21052717 |
Identification of 28 novel mutations in the Bardet-Biedl syndrome genes: the burden of private mutations in an extensively heterogeneous disease. | Muller J | Human genetics | 2010 | PMID: 20177705 |
Bardet-Biedl syndrome: an emerging pathomechanism of intracellular transport. | Blacque OE | Cellular and molecular life sciences : CMLS | 2006 | PMID: 16909204 |
Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. | Katsanis N | Science (New York, N.Y.) | 2001 | PMID: 11567139 |
Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2). | Nishimura DY | Human molecular genetics | 2001 | PMID: 11285252 |
- | - | - | - | DOI: doi:10.1155/2023/2564200 |
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Text-mined citations for rs121908176 ...
HelpRecord last updated Jun 29, 2025
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.