rs11024350

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001292063.2(OTOG):c.7645C>T(p.Leu2549Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,548,856 control chromosomes in the GnomAD database, including 13,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1165 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12634 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.29

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 11-17635139-C-T is Benign according to our data. Variant chr11-17635139-C-T is described in ClinVar as [Benign]. Clinvar id is 226911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17635139-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.7645C>T	p.Leu2549Leu	synonymous_variant	Exon 46 of 56	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.7681C>T	p.Leu2561Leu	synonymous_variant	Exon 45 of 55		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOG	ENST00000399397.6 link	c.7645C>T	p.Leu2549Leu	synonymous_variant	Exon 46 of 56	5	NM_001292063.2	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7 link	c.7681C>T	p.Leu2561Leu	synonymous_variant	Exon 45 of 55	5		ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2 link	n.4606-471C>T		intron_variant	Intron 19 of 21	2

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17885

AN:

151960

Hom.:

1166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0771

Gnomad AMI

AF:

0.254

Gnomad AMR

AF:

0.0931

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.133

AC:

18923

AN:

141776

Hom.:

1485

AF XY:

0.139

AC XY:

10687

AN XY:

76814

show subpopulations

Gnomad AFR exome

AF:

0.0756

Gnomad AMR exome

AF:

0.0685

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.250

Gnomad SAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.131

AC:

183533

AN:

1396778

Hom.:

12634

Cov.:

AF XY:

0.134

AC XY:

91989

AN XY:

688866

show subpopulations

Gnomad4 AFR exome

AF:

0.0809

Gnomad4 AMR exome

AF:

0.0709

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.213

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.118

AC:

17883

AN:

152078

Hom.:

1165

Cov.:

AF XY:

0.119

AC XY:

8827

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0770

Gnomad4 AMR

AF:

0.0929

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.130

Gnomad4 OTH

AF:

0.126

Alfa

AF:

0.127

Hom.:

1475

Bravo

AF:

0.112

Asia WGS

AF:

0.202

AC:

704

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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. -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Leu2561Leu in exon 45 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 18.5% (37/200) of H an Chinese chromosomes from a broad population by the 1000 Genomes Project (http ://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs11024350). -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.1

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over