ClinVar Genomic variation as it relates to human health
NM_006383.4(CIB2):c.97C>T (p.Arg33Ter)
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_006383.4(CIB2):c.97C>T (p.Arg33Ter)
Variation ID: 816953 Accession: VCV000816953.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 15q25.1 15: 78111266 (GRCh38) [ NCBI UCSC ] 15: 78403608 (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 Mar 16, 2020 Feb 14, 2024 Aug 25, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006383.4:c.97C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006374.1:p.Arg33Ter nonsense NM_001271888.2:c.-33C>T 5 prime UTR NM_001271889.2:c.52-1884C>T intron variant NM_001301224.2:c.87-1757C>T intron variant NC_000015.10:g.78111266G>A NC_000015.9:g.78403608G>A NG_033006.1:g.25270C>T - Protein change
- R33*
- Other names
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- Canonical SPDI
- NC_000015.10:78111265: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
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00004
The Genome Aggregation Database (gnomAD) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00006
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
- Links
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 | ||
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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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CIB2 | - | - |
GRCh38 GRCh37 |
192 | 231 |
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
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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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Aug 25, 2023 | RCV001007984.15 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 19, 2023 | RCV003155335.1 |
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
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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
(Feb 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003844979.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
Variant summary: CIB2 c.97C>T (p.Arg33X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: CIB2 c.97C>T (p.Arg33X) 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 within ClinVar (e.g. c.300_309del [p.Glu100fs]). The variant allele was found at a frequency of 6e-05 in 250814 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in CIB2 causing Usher Syndrome (6e-05 vs 0.0014), allowing no conclusion about variant significance. c.97C>T has been reported in the literature as a biallelic genotype in multiple individuals affected with Hearing Loss (e.g. Seco_2016, Talbi_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Aug 25, 2023)
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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: SCV001167716.4
First in ClinVar: Mar 16, 2020 Last updated: Aug 31, 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: 26173970, 30055715) (less)
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Pathogenic
(Oct 24, 2022)
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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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Invitae
Accession: SCV001414704.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 816953). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 816953). This premature translational stop signal has been observed in individual(s) with nonsyndromic hearing loss (PMID: 26173970). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs201845656, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg33*) in the CIB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CIB2 are known to be pathogenic (PMID: 26173970, 26226137, 26445815). (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808792.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953103.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001974613.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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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Genetic heterogeneity of congenital hearing impairment in Algerians from the Ghardaïa province. | Talbi S | International journal of pediatric otorhinolaryngology | 2018 | PMID: 30055715 |
Molecular genetics of cone-rod dystrophy in Chinese patients: New data from 61 probands and mutation overview of 163 probands. | Huang L | Experimental eye research | 2016 | PMID: 26992781 |
Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort. | Bademci G | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26226137 |
Novel and recurrent CIB2 variants, associated with nonsyndromic deafness, do not affect calcium buffering and localization in hair cells. | Seco CZ | European journal of human genetics : EJHG | 2016 | PMID: 26173970 |
Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran. | Sloan-Heggen CM | Journal of medical genetics | 2015 | PMID: 26445815 |
Text-mined citations for rs201845656 ...
HelpRecord last updated Feb 14, 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.