ClinVar Genomic variation as it relates to human health
NM_152384.3(BBS5):c.551A>G (p.Asn184Ser)
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.
Uncertain significance(1); Benign(1); Likely benign(5)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_152384.3(BBS5):c.551A>G (p.Asn184Ser)
Variation ID: 100605 Accession: VCV000100605.24
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 2q31.1 2: 169493769 (GRCh38) [ NCBI UCSC ] 2: 170350279 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Feb 25, 2014 Apr 15, 2024 Jan 31, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_152384.3:c.551A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689597.1:p.Asn184Ser missense NC_000002.12:g.169493769A>G NC_000002.11:g.170350279A>G NG_011567.1:g.19274A>G Q8N3I7:p.Asn184Ser - Protein change
- N184S
- Other names
- -
- Canonical SPDI
- NC_000002.12:169493768:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00220 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00220
1000 Genomes Project 30x 0.00234
Trans-Omics for Precision Medicine (TOPMed) 0.00346
The Genome Aggregation Database (gnomAD) 0.00380
The Genome Aggregation Database (gnomAD), exomes 0.00419
Exome Aggregation Consortium (ExAC) 0.00438
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00469
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
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
Help
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. |
|||
BBS5 | - | - |
GRCh38 GRCh37 |
329 | 385 |
Conditions - Germline
Condition
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Dec 1, 2023 | RCV000087001.19 | |
Likely pathogenic (1) |
no assertion criteria provided
|
Jan 1, 2015 | RCV000504860.9 | |
Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 13, 2023 | RCV000152843.23 | |
Benign (1) |
criteria provided, single submitter
|
Jan 31, 2024 | RCV001257073.14 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Oct 15, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000521323.5
First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023 |
Comment:
Identified in a patient with cone-rod dystrophy who also harbored two other variants in BBS5, although phase of these variants was unknown (Carss et al., … (more)
Identified in a patient with cone-rod dystrophy who also harbored two other variants in BBS5, although phase of these variants was unknown (Carss et al., 2017); Reported previously in the heterozygous state in multiple individuals with a ciliopathy phenotype; however, these individuals harbored pathogenic variants in other genes which likely explained their phenotype, suggesting that N184S may either not contribute, or be a potentially modifying variant, to the phenotype (Filges et al., 2014; Li et al., 2004; M'hamdi et al., 2014; Lindstrand et al., 2016; Jaffal et al., 2019); Published functional studies demonstrated defects on developmental in zebrafish (Castro-Sanchez et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29039417, 20498079, 15137946, 18203199, 22025579, 24128419, 23432027, 31506453, 28224992, 28041643, 29068140, 31888296, 27486776, 32581362) (less)
|
|
Likely benign
(Feb 13, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003844665.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
Variant summary: BBS5 c.551A>G (p.Asn184Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging … (more)
Variant summary: BBS5 c.551A>G (p.Asn184Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0042 in 251288 control chromosomes in the gnomAD database, including 2 homozygotes. The observed variant frequency is approximately 6.7 fold of the estimated maximal expected allele frequency for a pathogenic variant in BBS5 causing Bardet-Biedl Syndrome phenotype (0.00062), strongly suggesting that the variant is benign. The variant, c.551A>G, has been reported in the literature in individuals affected with Bardet-Biedl Syndrome, however in many cases it was found in heterozygous state, or together with other variants which could (potentially) explain the phenotype (e.g. Li_2004, Zaghoul_2010, Castro-Sanchez_2019, and the LOVD database). These reports do not provide unequivocal conclusions about association of the variant with Bardet-Biedl Syndrome. Publications reported experimental evidence evaluating an impact on protein and demonstrated developmental defects in zebrafish embryos (Zaghoul_2010, Castro-Sanchez_2019), however, these assays do not allow convincing conclusions about the variant effect humans. Five submitters have provided clinical-significance assessments for this variant in ClinVar after 2014, mostly without evidence for independent evaluation, and classified the variant as likely pathogenic (n=1), VUS (n=1), likely benign (n=2) / benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign. (less)
|
|
Likely benign
(Feb 22, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000609776.1
First in ClinVar: Feb 25, 2014 Last updated: Feb 25, 2014 |
|
|
Likely benign
(Apr 07, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000202239.7
First in ClinVar: Jan 29, 2015 Last updated: Nov 10, 2017 |
Number of individuals with the variant: 2
Sex: mixed
|
|
Likely benign
(Dec 18, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000246781.3
First in ClinVar: Oct 05, 2015 Last updated: Jun 15, 2020 |
|
|
Benign
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000255212.9
First in ClinVar: Oct 11, 2015 Last updated: Feb 14, 2024 |
|
|
Likely benign
(Dec 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004699369.2
First in ClinVar: Mar 10, 2024 Last updated: Apr 15, 2024 |
Comment:
BBS5: PP3, BS2
Number of individuals with the variant: 2
|
|
Likely pathogenic
(Jan 01, 2015)
|
no assertion criteria provided
Method: research
|
Cone-rod dystrophy
Affected status: yes
Allele origin:
unknown
|
NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV000598744.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: European
|
|
not provided
(-)
|
no classification provided
Method: not provided
|
not provided
Affected status: not provided
Allele origin:
not provided
|
NEI Ophthalmic Genomics Laboratory, National Institutes of Health
Accession: SCV000119254.1
First in ClinVar: Feb 25, 2014 Last updated: Feb 25, 2014 |
|
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 |
---|---|---|---|---|
Functional analysis of new human Bardet-Biedl syndrome loci specific variants in the zebrafish model. | Castro-Sánchez S | Scientific reports | 2019 | PMID: 31506453 |
Functional analyses of variants reveal a significant role for dominant negative and common alleles in oligogenic Bardet-Biedl syndrome. | Zaghloul NA | Proceedings of the National Academy of Sciences of the United States of America | 2010 | PMID: 20498079 |
Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. | Li JB | Cell | 2004 | PMID: 15137946 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BBS5 | - | - | - | - |
Text-mined citations for rs137853921 ...
HelpRecord last updated May 01, 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.