dbSNP rs2717482: OTOGL:p.Thr2152Thr (chr12-80367685-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001378609.3(OTOGL):c.6456G>A(p.Thr2152Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.93 in 1,487,130 control chromosomes in the GnomAD database, including 644,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68545 hom., cov: 32)

Exomes 𝑓: 0.93 ( 575559 hom. )

Consequence

OTOGL
NM_001378609.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.841

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 12-80367685-G-A is Benign according to our data. Variant chr12-80367685-G-A is described in ClinVar as [Benign]. Clinvar id is 226970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-80367685-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.841 with no splicing effect.

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.6456G>A	p.Thr2152Thr	synonymous_variant	Exon 54 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.6456G>A	p.Thr2152Thr	synonymous_variant	Exon 54 of 59	5	NM_001378609.3	ENSP00000447211.2		Q3ZCN5

Frequencies

GnomAD3 genomes

AF:

0.948

AC:

144249

AN:

152094

Hom.:

68493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.982

Gnomad AMI

AF:

0.940

Gnomad AMR

AF:

0.944

Gnomad ASJ

AF:

0.910

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:

0.938

GnomAD3 exomes

AF:

0.942

AC:

133550

AN:

141818

Hom.:

62944

AF XY:

0.938

AC XY:

71439

AN XY:

76142

show subpopulations

Gnomad AFR exome

AF:

0.984

Gnomad AMR exome

AF:

0.955

Gnomad ASJ exome

AF:

0.895

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.944

Gnomad FIN exome

AF:

0.970

Gnomad NFE exome

AF:

0.918

Gnomad OTH exome

AF:

0.921

GnomAD4 exome

AF:

0.928

AC:

1239245

AN:

1334918

Hom.:

575559

Cov.:

AF XY:

0.928

AC XY:

613494

AN XY:

660958

show subpopulations

Gnomad4 AFR exome

AF:

0.983

Gnomad4 AMR exome

AF:

0.953

Gnomad4 ASJ exome

AF:

0.903

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.947

Gnomad4 FIN exome

AF:

0.970

Gnomad4 NFE exome

AF:

0.921

Gnomad4 OTH exome

AF:

0.931

GnomAD4 genome

AF:

0.948

AC:

144358

AN:

152212

Hom.:

68545

Cov.:

AF XY:

0.951

AC XY:

70770

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.982

Gnomad4 AMR

AF:

0.944

Gnomad4 ASJ

AF:

0.910

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.946

Gnomad4 FIN

AF:

0.973

Gnomad4 NFE

AF:

0.924

Gnomad4 OTH

AF:

0.939

Alfa

AF:

0.932

Hom.:

24232

Bravo

AF:

0.948

Asia WGS

AF:

0.978

AC:

3391

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:6

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

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Thr2143Thr in exon 53 of OTOGL: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 7.9% (675/8584) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2717482). -

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. -

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

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

5.9

DANN

Benign

0.67

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

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