NM_001292063.2(OTOG):c.294C>G (p.Tyr98Ter) AND Autosomal recessive nonsyndromic hearing loss 18B

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 2, 2021
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:: RCV000593230.2

Allele description [Variation Report for NM_001292063.2(OTOG):c.294C>G (p.Tyr98Ter)]

NM_001292063.2(OTOG):c.294C>G (p.Tyr98Ter)

Gene:

OTOG:otogelin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_001292063.2(OTOG):c.294C>G (p.Tyr98Ter)

HGVS:

NC_000011.10:g.17553120C>G
NG_033191.2:g.10748C>G
NM_001277269.2:c.330C>G
NM_001292063.2:c.294C>GMANE SELECT
NP_001264198.1:p.Tyr110Ter
NP_001264198.1:p.Tyr110Ter
NP_001278992.1:p.Tyr98Ter
NC_000011.9:g.17574667C>G
NM_001277269.1:c.330C>G

Protein change:

Y110*

Links:

dbSNP: rs574007567

NCBI 1000 Genomes Browser:

rs574007567

Molecular consequence:

NM_001277269.2:c.330C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001292063.2:c.294C>G - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 18B
Synonyms:: Deafness, autosomal recessive 18b
Identifiers:: MONDO: MONDO:0013985; MedGen: C3554163; Orphanet: 90636; OMIM: 614945

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000693871	Laboratory of Molecular Genetics, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine	no assertion criteria provided	Pathogenic (Jun 9, 2017)	germline	clinical testing
SCV002012083	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 2, 2021)	paternal	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000693871

Laboratory of Molecular Genetics, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine

no assertion criteria provided

Pathogenic
(Jun 9, 2017)

germline

clinical testing

SCV002012083

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 2, 2021)

paternal

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	paternal	yes	1	not provided	not provided	1	not provided	clinical testing
East Asia	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratory of Molecular Genetics, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, SCV000693871.1

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

Description

The affected proband was five-year-old male and failed the newborn hearing screening with automated auditory brainstem response. At three months of age, the threshold of auditory brainstem response was 40 dB nHL at both ears. At 5 years of age, he had mild sensorineural hearing loss with decreased threshold in pure-tone audiometry (30 and 41 dB HL at the right and left ear, respectively). The audiogram was relatively flat pattern. In vestibular function test, the proband showed normoreflexia in caloric test as well as rotary chair test (with slow harmonic acceleration).

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

From 3billion, SCV002012083.1

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

Description

Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0000135, PM2). The variant has been reported as pathogenic (ClinVar ID: VCV000496812.1). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Dec 24, 2023

ClinVar

Relating variation to medicine