rs182000850

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001292063.2(OTOG):c.6326T>C(p.Val2109Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0029 in 1,550,626 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 103 hom. )

Consequence

OTOG
NM_001292063.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.42

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007984966).

BP6

Variant 11-17612653-T-C is Benign according to our data. Variant chr11-17612653-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 504839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17612653-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00569 (867/152258) while in subpopulation EAS AF= 0.0027 (14/5184). AF 95% confidence interval is 0.00163. There are 26 homozygotes in gnomad4. There are 639 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.6326T>C	p.Val2109Ala	missense_variant	Exon 38 of 56	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.6362T>C	p.Val2121Ala	missense_variant	Exon 37 of 55		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOG	ENST00000399397.6 link	c.6326T>C	p.Val2109Ala	missense_variant	Exon 38 of 56	5	NM_001292063.2	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7 link	c.6362T>C	p.Val2121Ala	missense_variant	Exon 37 of 55	5		ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2 link	n.3664T>C		non_coding_transcript_exon_variant	Exon 14 of 22	2

Frequencies

GnomAD3 genomes

AF:

0.00570

AC:

867

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0676

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00790

AC:

1178

AN:

149190

Hom.:

AF XY:

0.00691

AC XY:

555

AN XY:

80290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.000836

Gnomad EAS exome

AF:

0.00139

Gnomad SAS exome

AF:

0.000710

Gnomad FIN exome

AF:

0.0637

Gnomad NFE exome

AF:

0.000872

Gnomad OTH exome

AF:

0.00486

GnomAD4 exome

AF:

0.00260

AC:

3637

AN:

1398368

Hom.:

103

Cov.:

AF XY:

0.00252

AC XY:

1735

AN XY:

689712

show subpopulations

Gnomad4 AFR exome

AF:

0.0000949

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.00123

Gnomad4 EAS exome

AF:

0.00140

Gnomad4 SAS exome

AF:

0.000404

Gnomad4 FIN exome

AF:

0.0586

Gnomad4 NFE exome

AF:

0.000528

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00569

AC:

867

AN:

152258

Hom.:

Cov.:

AF XY:

0.00858

AC XY:

639

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0676

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.000642

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.00623

AC:

159

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OTOG: BS1:Supporting, BS2 -

Feb 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

May 09, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Val2121Ala in exon 37 of OTOG: This variant is not expected to have clinical s ignificance because it has been identified in 6.3% (1268/20104) of Finnish chrom osomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute. org; dbSNP rs182000850). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

T;T

MetaRNN

Benign

0.0080

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.7

D;.

REVEL

Benign

0.16

Sift

Benign

0.093

T;.

Sift4G

Uncertain

0.0020

D;D

Vest4

0.61

MVP

0.29

ClinPred

0.052

GERP RS

5.6

Varity_R

0.21

gMVP

0.63

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