NM_001292063.2:c.7062T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001292063.2(OTOG):c.7062T>C(p.Ser2354Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,550,302 control chromosomes in the GnomAD database, including 927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 296 hom., cov: 32)

Exomes 𝑓: 0.010 ( 631 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.92

Publications

1 publications found

Variant links:

Genes affected

OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

OTOG Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 18B
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

OTOG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-17632216-T-C is Benign according to our data. Variant chr11-17632216-T-C is described in ClinVar as [Benign]. Clinvar id is 226905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.7062T>C	p.Ser2354Ser	synonymous_variant	Exon 42 of 56	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.7098T>C	p.Ser2366Ser	synonymous_variant	Exon 41 of 55		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOG	ENST00000399397.6 link	c.7062T>C	p.Ser2354Ser	synonymous_variant	Exon 42 of 56	5	NM_001292063.2	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7 link	c.7098T>C	p.Ser2366Ser	synonymous_variant	Exon 41 of 55	5		ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2 link	n.4400T>C		non_coding_transcript_exon_variant	Exon 18 of 22	2

Frequencies

GnomAD3 genomes

AF:

0.0368

AC:

5596

AN:

152170

Hom.:

296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00200

Gnomad OTH

AF:

0.0263

GnomAD2 exomes

AF:

0.0219

AC:

3328

AN:

151620

AF XY:

0.0254

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.00611

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00601

Gnomad FIN exome

AF:

0.00126

Gnomad NFE exome

AF:

0.00198

Gnomad OTH exome

AF:

0.00985

GnomAD4 exome

AF:

0.0103

AC:

14382

AN:

1398014

Hom.:

631

Cov.:

AF XY:

0.0123

AC XY:

8453

AN XY:

689386

show subpopulations

African (AFR)

AF:

0.117

AC:

3700

AN:

31586

American (AMR)

AF:

0.00661

AC:

236

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.0128

AC:

322

AN:

25168

East Asian (EAS)

AF:

0.0109

AC:

388

AN:

35724

South Asian (SAS)

AF:

0.0874

AC:

6923

AN:

79230

European-Finnish (FIN)

AF:

0.00194

AC:

AN:

48486

Middle Eastern (MID)

AF:

0.0194

AC:

110

AN:

5668

European-Non Finnish (NFE)

AF:

0.00156

AC:

1684

AN:

1078490

Other (OTH)

AF:

0.0160

AC:

925

AN:

57970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

707

1414

2120

2827

3534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0368

AC:

5608

AN:

152288

Hom.:

296

Cov.:

AF XY:

0.0373

AC XY:

2778

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.110

AC:

4574

AN:

41532

American (AMR)

AF:

0.0139

AC:

212

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3472

East Asian (EAS)

AF:

0.0104

AC:

AN:

5176

South Asian (SAS)

AF:

0.103

AC:

498

AN:

4820

European-Finnish (FIN)

AF:

0.00188

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00200

AC:

136

AN:

68038

Other (OTH)

AF:

0.0293

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

248

496

743

991

1239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.0376

Asia WGS

AF:

0.0640

AC:

220

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ser2366Ser in exon 41 of OTOG: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 9.8% (19/194) of Lu hya (Kenyan) chromosomes from a broad population by the 1000 Genomes Project (ht tp://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs7114549). -

Oct 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

OTOG-related disorder

Benign:1

Jun 15, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.55

(source)

DANN

Benign

0.56

PhyloP100

-4.9

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001292063.2:c.7062T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over