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NM_006383.4(CIB2):c.556C>T (p.Arg186Trp) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 22, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001195601.4

Allele description [Variation Report for NM_006383.4(CIB2):c.556C>T (p.Arg186Trp)]

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

Gene:
CIB2:calcium and integrin binding family member 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q25.1
Genomic location:
Preferred name:
NM_006383.4(CIB2):c.556C>T (p.Arg186Trp)
HGVS:
  • NC_000015.10:g.78105319G>A
  • NG_033006.1:g.31217C>T
  • NM_001271888.2:c.427C>T
  • NM_001271889.2:c.409C>T
  • NM_001301224.2:c.571C>T
  • NM_006383.4:c.556C>TMANE SELECT
  • NP_001258817.1:p.Arg143Trp
  • NP_001258818.1:p.Arg137Trp
  • NP_001288153.1:p.Arg191Trp
  • NP_006374.1:p.Arg186Trp
  • NC_000015.9:g.78397661G>A
  • NM_006383.3:c.556C>T
  • NR_125435.2:n.764C>T
Protein change:
R137W
Links:
dbSNP: rs370359511
NCBI 1000 Genomes Browser:
rs370359511
Molecular consequence:
  • NM_001271888.2:c.427C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001271889.2:c.409C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301224.2:c.571C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006383.4:c.556C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_125435.2:n.764C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001366000Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Uncertain significance
(May 22, 2019) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown11not providednot providednot providedclinical testing

Citations

PubMed

A Novel C-Terminal CIB2 (Calcium and Integrin Binding Protein 2) Mutation Associated with Non-Syndromic Hearing Loss in a Hispanic Family.

Patel K, Giese AP, Grossheim JM, Hegde RS, Delio M, Samanich J, Riazuddin S, Frolenkov GI, Cai J, Ahmed ZM, Morrow BE.

PLoS One. 2015;10(10):e0133082. doi: 10.1371/journal.pone.0133082. Erratum in: PLoS One. 2015 Oct 16;10(10):e0141259. doi: 10.1371/journal.pone.0141259. Hegde, Rashima S [corrected to Hegde, Rashmi S].

PubMed [citation]
PMID:
26426422
PMCID:
PMC4591343

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV001366000.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p. Arg186Trp variant in CIB2 has been previously reported in the homozygous state in 1 Caribbean Hispanic individual with hearing loss and segregated with disease in 1 affected sibling, also homozygous for the variant (Patel 2015). This variant has been identified in 0.05% (13/24914) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is present in ClinVar (Variation ID 499480). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied: PM2_Supporting, PP1, PP3, PM3_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not provided1not provided

Last Updated: Oct 8, 2024