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NM_006383.4(CIB2):c.556C>T (p.Arg186Trp)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(1);Pathogenic(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Jul 28, 2021)
Last evaluated:
Jul 8, 2021
Accession:
VCV000499480.6
Variation ID:
499480
Description:
single nucleotide variant
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NM_006383.4(CIB2):c.556C>T (p.Arg186Trp)

Allele ID
490904
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q25.1
Genomic location
15: 78105319 (GRCh38) GRCh38 UCSC
15: 78397661 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.78105319G>A
NC_000015.9:g.78397661G>A
NM_006383.4:c.556C>T MANE Select NP_006374.1:p.Arg186Trp missense
... more HGVS
Protein change
R186W, R143W, R191W, R137W
Other names
-
Canonical SPDI
NC_000015.10:78105318:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.00040 (A)

Allele frequency
1000 Genomes Project 0.00040
Trans-Omics for Precision Medicine (TOPMed) 0.00034
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
The Genome Aggregation Database (gnomAD) 0.00019
Links
ClinGen: CA7680111
dbSNP: rs370359511
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Aug 20, 2020 RCV000596997.2
Uncertain significance 1 criteria provided, single submitter May 22, 2019 RCV001195601.1
Pathogenic 1 criteria provided, single submitter Jan 31, 2021 RCV001290343.1
Childhood onset hearing loss
Likely pathogenic 1 criteria provided, single submitter Jul 8, 2021 RCV001328027.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
CIB2 - - GRCh38
GRCh37
115 136

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jan 20, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000704978.2
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Uncertain significance
(May 22, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV001366000.1
Submitted: (May 14, 2020)
Evidence details
Publications
PubMed (1)
Comment:
Variant classified as Uncertain Significance - Favor Pathogenic. The p. Arg186Trp variant in CIB2 has been previously reported in the homozygous state in 1 Caribbean … (more)
Pathogenic
(Jan 31, 2021)
criteria provided, single submitter
Method: research
Deafness, autosomal recessive 48
(Autosomal recessive inheritance)
Allele origin: germline
Laboratory of Prof. Karen Avraham,Tel Aviv University
Accession: SCV001478331.1
Submitted: (Feb 04, 2021)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Aug 20, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Invitae
Accession: SCV001517809.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces arginine with tryptophan at codon 186 of the CIB2 protein (p.Arg186Trp). The arginine residue is highly conserved and there is a … (more)
Likely pathogenic
(Jul 08, 2021)
criteria provided, single submitter
Method: research
Childhood onset hearing loss
(Autosomal recessive inheritance)
Allele origin: germline
National Institute on Deafness and Communication Disorders,National Institutes of Health
Accession: SCV001519360.2
Submitted: (Jul 28, 2021)
Evidence details
Comment:
PS3_supporting, PM1, PM2_supporting, PM3_supporting, PP1_moderate / Modifications from PMID: 30311386 for classification: The genetic causes of hearing loss have not yet been well characterized in … (more)

Functional evidence

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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 this variant

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Title Author Journal Year Link
Variants in CIB2 cause DFNB48 and not USH1J. Booth KT Clinical genetics 2018 PMID: 29112224
CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells. Giese APJ Nature communications 2017 PMID: 28663585
A Novel C-Terminal CIB2 (Calcium and Integrin Binding Protein 2) Mutation Associated with Non-Syndromic Hearing Loss in a Hispanic Family. Patel K PloS one 2015 PMID: 26426422
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CIB2 - - - -

Text-mined citations for rs370359511...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 31, 2021