VCV000667428.5 - ClinVar

NC_000012.11:g.80632665_80732812del

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Likely pathogenic

This classification is based on the single submission received

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000012.11:g.80632665_80732812del

Variation ID: 667428 Accession: VCV000667428.5

Type and length

Deletion, 100,148 bp

Location

Cytogenetic: 12q21.31 12: 80632665-80732812 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Aug 26, 2019	Aug 26, 2019	Feb 27, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NC_000012.11:g.80632665_80732812del

Protein change

Other names

Canonical SPDI

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
OTOGL		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	1164	1185

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Rare genetic deafness	Likely pathogenic (1)	criteria provided, single submitter	Feb 27, 2019	RCV000826218.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Feb 27, 2019) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	Rare genetic deafness (Autosomal recessive inheritance)	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000967790.2 First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019	Comment: show The deletion of exons 9-41 (of 58 total exons) in the OTOGL gene has not been previously reported in individuals with hearing loss, but has been reported in four different studies in the Database of Genomic Variants with the highest frequency of 2/1109 samples (http://dgv.tcag.ca; Variants dgv1530n100, esv2761110, esv3580340, and esv3580340). Similar deletions have also been reported in ClinVar (Variation IDs 601318, 613849,396434). This deletion encompasses a substantial proportion of the coding region of the OTOGL gene and likely results in a truncated or absent protein. Loss of function of the OTOGL gene is an established disease mechanism for autosomal recessive hearing loss. Breakpoints of the deletion were observed in the NGS read data. In summary, this variant is likely pathogenic for recessive sensorineural hearing loss based on its predicted impact to the protein. ACMG/AMP criteria applied: PVS1, PM2_Supporting. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 1

Comment:

The deletion of exons 9-41 (of 58 total exons) in the OTOGL gene has not been previously reported in individuals with hearing loss, but has been reported in four different studies in the Database of Genomic Variants with the highest frequency of 2/1109 samples (http://dgv.tcag.ca; Variants dgv1530n100, esv2761110, esv3580340, and esv3580340). Similar deletions have also been reported in ClinVar (Variation IDs 601318, 613849,396434). This deletion encompasses a substantial proportion of the coding region of the OTOGL gene and likely results in a truncated or absent protein. Loss of function of the OTOGL gene is an established disease mechanism for autosomal recessive hearing loss. Breakpoints of the deletion were observed in the NGS read data. In summary, this variant is likely pathogenic for recessive sensorineural hearing loss based on its predicted impact to the protein. ACMG/AMP criteria applied: PVS1, PM2_Supporting.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Apr 08, 2025

ClinVar Genomic variation as it relates to human health

NC_000012.11:g.80632665_80732812del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for this variant ...