NM_194248.3(OTOF):c.5534-2A>G AND Autosomal recessive nonsyndromic hearing loss 9

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 29, 2020
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:: RCV001260331.1

Allele description [Variation Report for NM_194248.3(OTOF):c.5534-2A>G]

NM_194248.3(OTOF):c.5534-2A>G

Gene:

OTOF:otoferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p23.3

Genomic location:

Preferred name:

NM_194248.3(OTOF):c.5534-2A>G

HGVS:

NC_000002.12:g.26461032T>C
NG_009937.1:g.102667A>G
NG_094752.1:g.672T>C
NM_001287489.2:c.5534-2A>G
NM_004802.4:c.3233-2A>G
NM_194248.3:c.5534-2A>GMANE SELECT
NM_194322.3:c.3464-2A>G
NM_194323.3:c.3233-2A>G
NC_000002.11:g.26683900T>C
NM_194248.2:c.5534-2A>G

Links:

dbSNP: rs1664440809

NCBI 1000 Genomes Browser:

rs1664440809

Molecular consequence:

NM_001287489.2:c.5534-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004802.4:c.3233-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_194248.3:c.5534-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_194322.3:c.3464-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_194323.3:c.3233-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001437263	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Sep 29, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001437263

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Sep 29, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001437263.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: OTOF c.5534-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Computational tools predict a potential impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 247674 control chromosomes (gnomAD). To our knowledge, no occurrence of c.5534-2A>G in individuals affected with Nonsyndromic Hearing Loss And Deafness, Type 9 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 10, 2023

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