NM_001292063.2(OTOG):c.457_466del (p.Gly153fs) AND Rare genetic deafness

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 23, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV004018165.2

Allele description [Variation Report for NM_001292063.2(OTOG):c.457_466del (p.Gly153fs)]

NM_001292063.2(OTOG):c.457_466del (p.Gly153fs)

Gene:

OTOG:otogelin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_001292063.2(OTOG):c.457_466del (p.Gly153fs)

HGVS:

NC_000011.10:g.17553436_17553445del
NG_033191.2:g.11064_11073del
NM_001277269.2:c.493_502del
NM_001292063.2:c.457_466delMANE SELECT
NP_001264198.1:p.Gly165fs
NP_001278992.1:p.Gly153fs
NC_000011.10:g.17553436_17553445delGGGCTCTACT
NC_000011.9:g.17574983_17574992del

Protein change:

G153fs

Molecular consequence:

NM_001277269.2:c.493_502del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001292063.2:c.457_466del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Rare genetic deafness
Identifiers:: MedGen: C5680250; Orphanet: 96210

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004848665	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Jun 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004848665

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Jun 23, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848665.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The p.Gly165ThrfsX64 variant in OTOG has not been previously reported in individuals with nonsyndromic hearing loss and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 165 and leads to a premature termination codon 64 amino acids downstream. Loss of function of the OTOG gene is an established disease mechanism in autosomal recessive nonsyndromic hearing loss. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive nonsyndromic hearing loss. ACMG/AMP Criteria applied: PVS1, PM2_Supporting.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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