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NM_194248.3(OTOF):c.2215-1G>A AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 23, 2023
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:
RCV003698818.2

Allele description [Variation Report for NM_194248.3(OTOF):c.2215-1G>A]

NM_194248.3(OTOF):c.2215-1G>A

Gene:
OTOF:otoferlin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p23.3
Genomic location:
Preferred name:
NM_194248.3(OTOF):c.2215-1G>A
HGVS:
  • NC_000002.12:g.26477750C>T
  • NG_009937.1:g.85949G>A
  • NG_166359.1:g.292C>T
  • NM_001287489.2:c.2215-1G>A
  • NM_004802.4:c.-27-1G>A
  • NM_194248.3:c.2215-1G>AMANE SELECT
  • NM_194322.3:c.144G>A
  • NM_194323.3:c.-27-1G>A
  • NP_919303.1:p.Gln48=
  • NC_000002.11:g.26700618C>T
  • NM_194248.2:c.2215-1G>A
Links:
dbSNP: rs1558486388
NCBI 1000 Genomes Browser:
rs1558486388
Molecular consequence:
  • NM_001287489.2:c.2215-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_004802.4:c.-27-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_194248.3:c.2215-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_194323.3:c.-27-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_194322.3:c.144G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004459597Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Apr 23, 2023)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder.

Zhang QJ, Han B, Lan L, Zong L, Shi W, Wang HY, Xie LY, Wang H, Zhao C, Zhang C, Yin ZF, Wang DY, Petit C, Guan J, Wang QJ.

Clin Genet. 2016 Sep;90(3):238-46. doi: 10.1111/cge.12744. Epub 2016 Mar 11.

PubMed [citation]
PMID:
26818607

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004459597.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 632358). Disruption of this splice site has been observed in individual(s) with congenital auditory neuropathy spectrum disorder (PMID: 26818607). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 18 of the OTOF gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in OTOF are known to be pathogenic (PMID: 18381613, 19250381, 22575033).

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

Last Updated: Sep 29, 2024