ClinVar Genomic variation as it relates to human health
NM_152384.3(BBS5):c.214G>A (p.Gly72Ser)
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_152384.3(BBS5):c.214G>A (p.Gly72Ser)
Variation ID: 6161 Accession: VCV000006161.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q31.1 2: 169487811 (GRCh38) [ NCBI UCSC ] 2: 170344321 (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 28, 2017 Apr 6, 2024 Mar 14, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152384.3:c.214G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689597.1:p.Gly72Ser missense NC_000002.12:g.169487811G>A NC_000002.11:g.170344321G>A NG_011567.1:g.13316G>A Q8N3I7:p.Gly72Ser - Protein change
- G72S
- Other names
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- Canonical SPDI
- NC_000002.12:169487810: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
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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BBS5 | - | - |
GRCh38 GRCh37 |
333 | 389 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Likely pathogenic (2) |
criteria provided, single submitter
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Mar 14, 2024 | RCV000006536.7 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Nov 6, 2023 | RCV000787535.4 |
Submissions - Germline
Classification
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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
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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
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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
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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
(Nov 06, 2023)
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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: SCV003027436.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 72 of the BBS5 protein (p.Gly72Ser). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 72 of the BBS5 protein (p.Gly72Ser). This variant is present in population databases (rs121908581, gnomAD 0.01%). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 18203199). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6161). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BBS5 protein function with a positive predictive value of 80%. 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
(Oct 05, 2021)
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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: SCV002015184.1
First in ClinVar: Nov 20, 2021 Last updated: Nov 20, 2021 |
Comment:
Variant summary: BBS5 c.214G>A (p.Gly72Ser) results in a non-conservative amino acid change located in the first DM16 repeat (IPR014003) of the encoded protein sequence. Five … (more)
Variant summary: BBS5 c.214G>A (p.Gly72Ser) results in a non-conservative amino acid change located in the first DM16 repeat (IPR014003) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.7e-06 in 149692 control chromosomes (gnomAD v3.1, genomes dataset). The variant, c.214G>A, has been reported in the literature in multiple homozygous individuals of African origin, who were affected with Bardet-Biedl Syndrome (Hjortshoj_2008, Janssen_2011, Jespersgaard_2019, Habibi_2020). These data indicate that the variant is very likely to be associated with disease. At least one publication also reported experimental evidence, and demonstrated that the variant affected ciliogenesis and impaired hedgehog signaling in fibroblasts that were derived from homozygous patients (Brunbjerg Hey_2021). One submitter has provided clinical-significance assessment for this variant in ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Mar 14, 2024)
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criteria provided, single submitter
Method: research
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Bardet-Biedl syndrome 5
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004801257.2
First in ClinVar: Mar 16, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Feb 15, 2008)
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no assertion criteria provided
Method: literature only
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BARDET-BIEDL SYNDROME 5
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000026719.3
First in ClinVar: Apr 04, 2013 Last updated: Aug 28, 2017 |
Comment on evidence:
In 4 affected sibs of a Somali family with Bardet-Biedl syndrome (BBS5; 615983), Hjortshoj et al. (2008) identified a homozygous 214G-A transition in exon 4 … (more)
In 4 affected sibs of a Somali family with Bardet-Biedl syndrome (BBS5; 615983), Hjortshoj et al. (2008) identified a homozygous 214G-A transition in exon 4 of the BBS5 gene, resulting in a gly72-to-ser (G72S) substitution. Each unaffected parent was heterozygous for the mutation, which was not identified in 202 ethnically matched controls. (less)
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Pathogenic
(Apr 01, 2018)
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no assertion criteria provided
Method: research
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Bardet-Biedl syndrome
Affected status: yes
Allele origin:
unknown
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Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926507.2 First in ClinVar: Jul 21, 2019 Last updated: Sep 03, 2023 |
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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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BBS Proteins Affect Ciliogenesis and Are Essential for Hedgehog Signaling, but Not for Formation of iPSC-Derived RPE-65 Expressing RPE-Like Cells. | Hey CAB | International journal of molecular sciences | 2021 | PMID: 33572860 |
Genetic spectrum of retinal dystrophies in Tunisia. | Habibi I | Scientific reports | 2020 | PMID: 32641690 |
Generation and characterization of three isogenic induced pluripotent stem cell lines from a patient with Bardet-Biedl syndrome and homozygous for the BBS5 variant. | Hey CAB | Stem cell research | 2019 | PMID: 31760295 |
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. | Jespersgaard C | Scientific reports | 2019 | PMID: 30718709 |
Mutation analysis in Bardet-Biedl syndrome by DNA pooling and massively parallel resequencing in 105 individuals. | Janssen S | Human genetics | 2011 | PMID: 21052717 |
Novel mutations in BBS5 highlight the importance of this gene in non-Caucasian Bardet-Biedl syndrome patients. | Hjortshøj TD | American journal of medical genetics. Part A | 2008 | PMID: 18203199 |
Text-mined citations for rs121908581 ...
HelpRecord last updated Apr 06, 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.