rs2034528

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_StrongBA1

The NM_001378609.3(OTOGL):c.6247A>G(p.Ile2083Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 1,505,062 control chromosomes in the GnomAD database, including 649,613 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67607 hom., cov: 32)

Exomes 𝑓: 0.93 ( 582006 hom. )

Consequence

OTOGL
NM_001378609.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.553

Variant links:

Genes affected

OTOGL (HGNC:26901): (otogelin like) The protein encoded by this gene belongs to the otogelin family. This gene is expressed in the inner ear of vertebrates with the highest level of expression seen at the embryonic stage and lowest in adult. Knockdown studies in zebrafish suggest that this gene is essential for normal inner ear function. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2012]

OTOGL 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=6.47368E-7).

BP6

Variant 12-80358880-A-G is Benign according to our data. Variant chr12-80358880-A-G is described in ClinVar as [Benign]. Clinvar id is 226966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80358880-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOGL	NM_001378609.3 link	c.6247A>G	p.Ile2083Val	missense_variant	Exon 52 of 59	ENST00000547103.7	NP_001365538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOGL	ENST00000547103.7 link	c.6247A>G	p.Ile2083Val	missense_variant	Exon 52 of 59	5	NM_001378609.3	ENSP00000447211.2		Q3ZCN5

Frequencies

GnomAD3 genomes

AF:

0.942

AC:

143322

AN:

152162

Hom.:

67568

Cov.:

show subpopulations

Gnomad AFR

AF:

0.961

Gnomad AMI

AF:

0.940

Gnomad AMR

AF:

0.941

Gnomad ASJ

AF:

0.901

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.947

Gnomad FIN

AF:

0.973

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.924

Gnomad OTH

AF:

0.934

GnomAD3 exomes

AF:

0.941

AC:

139151

AN:

147890

Hom.:

65523

AF XY:

0.939

AC XY:

73229

AN XY:

77972

show subpopulations

Gnomad AFR exome

AF:

0.962

Gnomad AMR exome

AF:

0.957

Gnomad ASJ exome

AF:

0.895

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.949

Gnomad FIN exome

AF:

0.971

Gnomad NFE exome

AF:

0.921

Gnomad OTH exome

AF:

0.922

GnomAD4 exome

AF:

0.927

AC:

1254466

AN:

1352782

Hom.:

582006

Cov.:

AF XY:

0.927

AC XY:

620823

AN XY:

669428

show subpopulations

Gnomad4 AFR exome

AF:

0.959

Gnomad4 AMR exome

AF:

0.955

Gnomad4 ASJ exome

AF:

0.893

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.948

Gnomad4 FIN exome

AF:

0.970

Gnomad4 NFE exome

AF:

0.921

Gnomad4 OTH exome

AF:

0.929

GnomAD4 genome

AF:

0.942

AC:

143416

AN:

152280

Hom.:

67607

Cov.:

AF XY:

0.944

AC XY:

70315

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.960

Gnomad4 AMR

AF:

0.941

Gnomad4 ASJ

AF:

0.901

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.947

Gnomad4 FIN

AF:

0.973

Gnomad4 NFE

AF:

0.924

Gnomad4 OTH

AF:

0.935

Alfa

AF:

0.923

Hom.:

91338

Bravo

AF:

0.941

TwinsUK

AF:

0.921

AC:

3415

ALSPAC

AF:

0.927

AC:

3571

ESP6500AA

AF:

0.959

AC:

4160

ESP6500EA

AF:

0.924

AC:

7815

ExAC

AF:

0.928

AC:

76951

Asia WGS

AF:

0.976

AC:

3388

AN:

3472

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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 11, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ile2074Val in exon 51 of OTOGL: This variant is not expected to have clinical si gnificance because it has been identified in 7.6% (641/8456) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs2034528). -

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

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_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.8

DANN

Benign

0.29

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.16

T;.;T

MetaRNN

Benign

6.5e-7

T;T;T

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.33

PROVEAN

Benign

0.50

.;.;N

REVEL

Benign

0.026

Sift

Benign

1.0

.;.;T

Sift4G

Benign

1.0

.;.;T

Vest4

0.058

MPC

0.021

ClinPred

0.00015

GERP RS

0.35

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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