NM_001292063.2(OTOG):c.7585+2T>C AND Rare genetic deafness

Clinical significance:Likely pathogenic (Last evaluated: Oct 6, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000603000.1

Allele description [Variation Report for NM_001292063.2(OTOG):c.7585+2T>C]

NM_001292063.2(OTOG):c.7585+2T>C

Gene:
OTOG:otogelin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.1
Genomic location:
Preferred name:
NM_001292063.2(OTOG):c.7585+2T>C
HGVS:
  • NC_000011.10:g.17634950T>C
  • NG_033191.2:g.92578T>C
  • NM_001277269.1:c.7621+2T>C
  • NM_001277269.2:c.7621+2T>C
  • NM_001292063.2:c.7585+2T>CMANE SELECT
  • NC_000011.9:g.17656497T>C
  • NC_000011.9:g.17656497T>C
Links:
dbSNP: rs1401870617
NCBI 1000 Genomes Browser:
rs1401870617
Molecular consequence:
  • NM_001277269.1:c.7621+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001277269.2:c.7621+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001292063.2:c.7585+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
1

Condition(s)

Name:
Rare genetic deafness
Identifiers:
MedGen: CN826980; Orphanet: 96210

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000712465Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Oct 6, 2016)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

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, Partners HealthCare Personalized Medicine, SCV000712465.2

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

Description

The c.7621+2T>C variant in OTOG has not been previously reported in individuals with hearing loss. Data from large population studies is insufficient to assess the frequency of this variant. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicin g leading to an abnormal or absent protein. Two loss of function variants in the OTOG gene have been reported to segregate with hearing loss in two families (Sc hraders 2012), and disruption of Otog in mice resulted in deafness supporting of a loss-of-function mechanism for the disease (Simmler 2000). In summary, althou gh additional evidence is required to strengthen the gene-disease association be tween OTOG and hearing loss, currently available data support that the c.7621+2T >C variant is likely pathogenic.

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

Last Updated: Oct 25, 2021

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