rs2023483

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.8364G>C(p.Leu2788Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,548,636 control chromosomes in the GnomAD database, including 81,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10263 hom., cov: 33)

Exomes 𝑓: 0.31 ( 71491 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -4.72

Publications

10 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=-0.74).

BP6

Variant 11-17642195-G-C is Benign according to our data. Variant chr11-17642195-G-C is described in ClinVar as Benign. ClinVar VariationId is 226919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.8364G>C	p.Leu2788Leu	synonymous_variant	Exon 53 of 56	ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2 link	c.8400G>C	p.Leu2800Leu	synonymous_variant	Exon 52 of 55		NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6 link	c.8364G>C	p.Leu2788Leu	synonymous_variant	Exon 53 of 56	5	NM_001292063.2	ENSP00000382329.2
OTOG	ENST00000399391.7 link	c.8400G>C	p.Leu2800Leu	synonymous_variant	Exon 52 of 55	5		ENSP00000382323.2

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53536

AN:

151936

Hom.:

10241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.506

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.319

GnomAD2 exomes

AF:

0.295

AC:

43244

AN:

146758

AF XY:

0.305

show subpopulations

Gnomad AFR exome

AF:

0.520

Gnomad AMR exome

AF:

0.170

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.294

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.314

AC:

437880

AN:

1396582

Hom.:

71491

Cov.:

AF XY:

0.316

AC XY:

217337

AN XY:

688682

show subpopulations

African (AFR)

AF:

0.521

AC:

16443

AN:

31538

American (AMR)

AF:

0.179

AC:

6364

AN:

35584

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

6363

AN:

25116

East Asian (EAS)

AF:

0.159

AC:

5663

AN:

35692

South Asian (SAS)

AF:

0.405

AC:

31980

AN:

78942

European-Finnish (FIN)

AF:

0.290

AC:

13948

AN:

48092

Middle Eastern (MID)

AF:

0.245

AC:

1397

AN:

5692

European-Non Finnish (NFE)

AF:

0.313

AC:

337774

AN:

1078002

Other (OTH)

AF:

0.310

AC:

17948

AN:

57924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

16193

32385

48578

64770

80963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11354

22708

34062

45416

56770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.353

AC:

53605

AN:

152054

Hom.:

10263

Cov.:

AF XY:

0.350

AC XY:

26017

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.507

AC:

21012

AN:

41480

American (AMR)

AF:

0.248

AC:

3783

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

848

AN:

3464

East Asian (EAS)

AF:

0.180

AC:

926

AN:

5158

South Asian (SAS)

AF:

0.411

AC:

1978

AN:

4812

European-Finnish (FIN)

AF:

0.290

AC:

3077

AN:

10594

Middle Eastern (MID)

AF:

0.271

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.310

AC:

21034

AN:

67950

Other (OTH)

AF:

0.320

AC:

677

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1710

3420

5131

6841

8551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.314

Hom.:

1466

Bravo

AF:

0.348

Asia WGS

AF:

0.349

AC:

1215

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Leu2800Leu in exon 52 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 58.8% (114/194) of Luhya (Kenyan) chromosomes from a broad population by the 1000 Genomes Project ( http://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs2023483). -

May 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 18B

Benign:1

May 18, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.0060

(source)

DANN

Benign

0.64

PhyloP100

-4.7

Mutation Taster

=100/0

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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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