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NM_194248.3(OTOF):c.2348del (p.Gly783fs) AND Autosomal recessive nonsyndromic hearing loss 9

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Apr 22, 2022
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:
RCV000021046.12

Allele description [Variation Report for NM_194248.3(OTOF):c.2348del (p.Gly783fs)]

NM_194248.3(OTOF):c.2348del (p.Gly783fs)

Gene:
OTOF:otoferlin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p23.3
Genomic location:
Preferred name:
NM_194248.3(OTOF):c.2348del (p.Gly783fs)
HGVS:
  • NC_000002.11:g.26700342del
  • NC_000002.12:g.26477476del
  • NG_009937.1:g.86225del
  • NM_001287489.2:c.2348del
  • NM_004802.4:c.107del
  • NM_194248.3:c.2348delMANE SELECT
  • NM_194322.3:c.278del
  • NM_194323.3:c.107del
  • NP_001274418.1:p.Gly783fs
  • NP_004793.2:p.Gly36fs
  • NP_919224.1:p.Gly783fs
  • NP_919303.1:p.Gly93fs
  • NP_919304.1:p.Gly36fs
  • NC_000002.11:g.26700342del
  • NC_000002.11:g.26700342delC
  • NC_000002.11:g.26700344del
  • NM_194248.1:c.2348delG
  • NM_194248.2:c.2348delG
  • NM_194248.3:c.2348delGMANE SELECT
  • c.2348delG
  • p.Gly783AlafsX17
Protein change:
G36fs
Links:
dbSNP: rs80356591
NCBI 1000 Genomes Browser:
rs80356591
Molecular consequence:
  • NM_001287489.2:c.2348del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004802.4:c.107del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_194248.3:c.2348del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_194322.3:c.278del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_194323.3:c.107del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Autosomal recessive nonsyndromic hearing loss 9
Synonyms:
NEUROSENSORY NONSYNDROMIC RECESSIVE DEAFNESS 9; Deafness, autosomal recessive 9; AUDITORY NEUROPATHY, AUTOSOMAL RECESSIVE, 1, TEMPERATURE-SENSITIVE; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010986; MedGen: C1832828; Orphanet: 90636; OMIM: 601071

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000041700GeneReviews
no classification provided
not providedunknownliterature only

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

SCV002503775Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Apr 22, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownnot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene.

Varga R, Kelley PM, Keats BJ, Starr A, Leal SM, Cohn E, Kimberling WJ.

J Med Genet. 2003 Jan;40(1):45-50. No abstract available.

PubMed [citation]
PMID:
12525542
PMCID:
PMC1735255

OTOF-Related Deafness.

Azaiez H, Thorpe RK, Smith RJH.

2008 Feb 29 [updated 2021 Jan 21]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]
PMID:
20301429
See all PubMed Citations (5)

Details of each submission

From GeneReviews, SCV000041700.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownnot providednot providednot providedAssert pathogenicitynot providednot providednot providednot provided

From Molecular Genetics, Royal Melbourne Hospital, SCV002503775.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change is a deletion of 1 bp in exon 20 (of 46) of OTOF that is predicted to create a premature termination codon at position 799, p.(Gly783Alafs*17), which is expected to result in an absent or disrupted protein product. Loss of function is an established mechanism for disease for this gene. The variant is present in a large population cohort at a frequency of 0.005% (rs80356591, 12/262,222 alleles, 0 homozygotes in gnomAD v2.1), with a frequency of 0.02% in the African subpopulation (4/22,908 alleles, 0 homozygotes). The variant has been identified compound heterozygous with a second pathogenic allele in at least two individuals with non-syndromic auditory neuropathy (PMID: 16371502, 19461658). Based on the classification scheme RMH ACMG Guidelines v1.2.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM3_Strong.

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

Last Updated: Apr 15, 2024