NM_144672.4(OTOA):c.1765del (p.Gln589fs) AND Autosomal recessive nonsyndromic hearing loss 22

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 13, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000845108.3

Allele description [Variation Report for NM_144672.4(OTOA):c.1765del (p.Gln589fs)]

NM_144672.4(OTOA):c.1765del (p.Gln589fs)

Gene:

OTOA:otoancorin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_144672.4(OTOA):c.1765del (p.Gln589fs)

HGVS:

NC_000016.10:g.21719463del
NG_012973.2:g.60331del
NM_001161683.2:c.1528del
NM_144672.4:c.1765delMANE SELECT
NM_170664.3:c.793del
NP_001155155.1:p.Gln510fs
NP_653273.3:p.Gln589fs
NP_733764.1:p.Gln265fs
NC_000016.9:g.21730783del
NC_000016.9:g.21730784del
NC_000016.9:g.21730784delC
NG_012973.1:g.45950del
NM_144672.3:c.1764delC
NM_144672.4:c.1765delCMANE SELECT

Protein change:

Q265fs

Links:

dbSNP: rs775776282

NCBI 1000 Genomes Browser:

rs775776282

Molecular consequence:

NM_001161683.2:c.1528del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_144672.4:c.1765del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_170664.3:c.793del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 22
Synonyms:: Deafness, autosomal recessive 22
Identifiers:: MONDO: MONDO:0011762; MedGen: C1846896; Orphanet: 90636; OMIM: 607039

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000930662	Laboratory of Molecular Genetics, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine	no assertion criteria provided	Pathogenic (Aug 8, 2019)	germline	research
SCV002521528	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25373420, 25741868
SCV002762666	Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	criteria provided, single submitter (ClinGen HL ACMG Specifications v1)	Pathogenic (Dec 13, 2022)	unknown	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

SCV000930662

Laboratory of Molecular Genetics, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine

no assertion criteria provided

Pathogenic
(Aug 8, 2019)

germline

research

SCV002521528

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 22, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002762666

Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital

criteria provided, single submitter

(ClinGen HL ACMG Specifications v1)

Pathogenic
(Dec 13, 2022)

unknown

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	yes	1	not provided	not provided	1	not provided	clinical testing
Han Chinese	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing
Korean	germline	yes	not provided	0	not provided	not provided	not provided	research

Citations

PubMed

Exploration of molecular genetic etiology for Korean cochlear implantees with severe to profound hearing loss and its implication.

Park JH, Kim NK, Kim AR, Rhee J, Oh SH, Koo JW, Nam JY, Park WY, Choi BY.

Orphanet J Rare Dis. 2014 Nov 6;9:167. doi: 10.1186/s13023-014-0167-8.

PubMed [citation]

PMID:: 25373420
PMCID:: PMC4243193

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

See all PubMed Citations (3)

Details of each submission

From Laboratory of Molecular Genetics, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, SCV000930662.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Korean	not provided	not provided	not provided	research	not provided

Description

In a family with NSHL, homozygous frameshift variants in OTOA were found. ARNSHL had a characteristic of severe hearing loss. Age of onset was prelingual.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	0	not provided

From 3billion, SCV002521528.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with OTOA related disorder (ClinVar ID: VCV000684616 / PMID: 25373420 / 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

From Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, SCV002762666.1

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

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

Last Updated: Sep 29, 2024

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