ClinVar Genomic variation as it relates to human health
NM_031885.5(BBS2):c.534+1G>T
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.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_031885.5(BBS2):c.534+1G>T
Variation ID: 553927 Accession: VCV000553927.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16q13 16: 56510858 (GRCh38) [ NCBI UCSC ] 16: 56544770 (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 Aug 5, 2018 Feb 28, 2024 Jan 24, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_031885.5:c.534+1G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001377456.1:c.534+1G>T splice donor NC_000016.10:g.56510858C>A NC_000016.9:g.56544770C>A NG_009312.2:g.14167G>T - Protein change
- Other names
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- Canonical SPDI
- NC_000016.10:56510857:C: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00003
The Genome Aggregation Database (gnomAD) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00010
Exome Aggregation Consortium (ExAC) 0.00012
- 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
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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 |
1088 | 1121 |
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
Help
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 (6) |
criteria provided, multiple submitters, no conflicts
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Oct 25, 2023 | RCV000669469.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 8, 2022 | RCV000762968.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 24, 2024 | RCV000694960.7 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Feb 20, 2018 | RCV001075332.1 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Aug 25, 2021 | RCV001784258.4 |
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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Likely pathogenic
(Feb 20, 2018)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001240950.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
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Pathogenic
(May 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Bardet-Biedl syndrome 2
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002521604.1
First in ClinVar: Jun 03, 2022 Last updated: Jun 03, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.010%). Canonical splice site: predicted to alter splicing … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.010%). Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000553927). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Rod-cone dystrophy (present)
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Pathogenic
(Nov 03, 2021)
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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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Myriad Genetics, Inc.
Accession: SCV002060393.2
First in ClinVar: Jan 15, 2022 Last updated: Nov 29, 2022 |
Comment:
NM_031885.3(BBS2):c.534+1G>T is a canonical splice variant classified as pathogenic in the context of Bardet-Biedl syndrome, BBS2-related. c.534+1G>T has been observed in cases with relevant disease … (more)
NM_031885.3(BBS2):c.534+1G>T is a canonical splice variant classified as pathogenic in the context of Bardet-Biedl syndrome, BBS2-related. c.534+1G>T has been observed in cases with relevant disease (PMID: 24280758, 33520300, 33777945). Functional assessments of this variant are not available in the literature. c.534+1G>T has been observed in population frequency databases (gnomAD: EAS 0.14%). In summary, NM_031885.3(BBS2):c.534+1G>T is a canonical splice variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Feb 08, 2022)
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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: SCV000893409.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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Pathogenic
(Oct 25, 2023)
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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: SCV004213982.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Aug 25, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002022020.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 24, 2024)
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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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Invitae
Accession: SCV000823431.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 2024 |
Comment:
This sequence change affects a donor splice site in intron 4 of the BBS2 gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects a donor splice site in intron 4 of the BBS2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BBS2 are known to be pathogenic (PMID: 11285252, 20177705, 24608809, 26518167). This variant is present in population databases (rs773862084, gnomAD 0.1%). Disruption of this splice site has been observed in individual(s) with Bardet-Biedl syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 553927). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 16, 2020)
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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: SCV001458473.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: literature only
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Bardet-Biedl syndrome 2
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
biparental
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Department of Traditional Chinese Medicine, Fujian Provincial Hospital
Accession: SCV004046863.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is a rare, autosomal recessive inherited, genetic syndrome, which involves multiple … (more)
This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is a rare, autosomal recessive inherited, genetic syndrome, which involves multiple systems with diverse clinical manifestations, high disability rate and poor prognosis characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. However, in this study, not only the proband who was homozygous mutation carriers showed typical retinitis pigmentation, polydactylism, obesity, bicornuate uterus, left renal dysplasia, hypogonadism and progressive renal dysfunction, but also those heterozygous mutation carriers in the family, manifests unequal development of both kidneys, gonadal hypoplasia and dilated cardiomyopathy, which were intermediate traits. Sequencing of the RT-PCR products from the proband’s blood sample reveals a 824-nucleotide (nt) insertion exists at the junction between exons 4 and 5 of the BBS2 cDNA. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Bardet-Biedl syndrome 2
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Department of Pediatrics, National Cheng-Kung University Hospital
Accession: SCV004042735.2
First in ClinVar: Oct 21, 2023 Last updated: Jan 26, 2024 |
Comment:
The c.534+1 G>T variant in BBS2 has been previously reported in BBS2 patients in several studies investigating syndromic ciliopathy. The variant was found in several … (more)
The c.534+1 G>T variant in BBS2 has been previously reported in BBS2 patients in several studies investigating syndromic ciliopathy. The variant was found in several of our patients with obesity, visual impairment, polydactyly, and renal disease, which are compatible with the BBS2 phenotype. Until now, there has not been an in vitro functional study to indicate the variant’s pathogenicity. However, it is a splice site mutation predicted to cause exon skipping, and multiple computational predictive software support its pathogenicity. In summary, the c.534+1 G>T variant in BBS2 meets the criteria of ACMG/AMP guidelines to be classified as pathogenic based on the clinical information. (less)
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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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Ocular Characteristics of Patients With Bardet-Biedl Syndrome Caused by Pathogenic BBS Gene Variation in a Chinese Cohort. | Meng X | Frontiers in cell and developmental biology | 2021 | DOI: 10.3389/fcell.2021.635216 |
Ocular Characteristics of Patients With Bardet-Biedl Syndrome Caused by Pathogenic BBS Gene Variation in a Chinese Cohort. | Meng X | Frontiers in cell and developmental biology | 2021 | PMID: 33777945 |
Novel Compound Heterozygous BBS2 and Homozygous MKKS Variants Detected in Chinese Families with Bardet-Biedl Syndrome. | Huang L | Journal of ophthalmology | 2021 | DOI: 10.1155/2021/6751857 |
Novel Compound Heterozygous BBS2 and Homozygous MKKS Variants Detected in Chinese Families with Bardet-Biedl Syndrome. | Huang L | Journal of ophthalmology | 2021 | PMID: 33520300 |
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. | Nykamp K | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | DOI: 10.1038/gim.2017.37 |
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 |
Comprehensive molecular diagnosis of Bardet-Biedl syndrome by high-throughput targeted exome sequencing. | Xing DJ | PloS one | 2014 | PMID: 24608809 |
The case: hexadactyly, blindness, obesity, and end-stage renal disease. | Wang KY | Kidney international | 2013 | PMID: 24280758 |
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 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2). | Nishimura DY | Human molecular genetics | 2001 | PMID: 11285252 |
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Text-mined citations for rs773862084 ...
HelpRecord last updated Mar 17, 2024
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.