NM_144672.4(OTOA):c.1879C>T (p.Pro627Ser) AND Autosomal recessive nonsyndromic hearing loss 22

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 1, 2023
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:: RCV000087055.4

Allele description [Variation Report for NM_144672.4(OTOA):c.1879C>T (p.Pro627Ser)]

NM_144672.4(OTOA):c.1879C>T (p.Pro627Ser)

Gene:

OTOA:otoancorin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_144672.4(OTOA):c.1879C>T (p.Pro627Ser)

HGVS:

NC_000016.10:g.21722977C>T
NG_012973.2:g.63845C>T
NM_001161683.2:c.1642C>T
NM_144672.4:c.1879C>TMANE SELECT
NM_170664.3:c.907C>T
NP_001155155.1:p.Pro548Ser
NP_653273.3:p.Pro627Ser
NP_733764.1:p.Pro303Ser
NC_000016.9:g.21734298C>T
NG_012973.1:g.49464C>T
NM_144672.3:c.1879C>T

Protein change:

P303S; PRO627SER

Links:

OMIM: 607038.0004; dbSNP: rs587777133

NCBI 1000 Genomes Browser:

rs587777133

Molecular consequence:

NM_001161683.2:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_144672.4:c.1879C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170664.3:c.907C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000119869	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV003918902	Payam Genetics Center, General Welfare Department of North Khorasan Province	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 1, 2023)	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

SCV000119869

OMIM

no assertion criteria provided

Pathogenic
(Sep 1, 2013)

germline

literature only

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

SCV003918902

Payam Genetics Center, General Welfare Department of North Khorasan Province

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 1, 2023)

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
Iranian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel OTOA mutations cause autosomal recessive non-syndromic hearing impairment in Pakistani families.

Lee K, Chiu I, Santos-Cortez RL, Basit S, Khan S, Azeem Z, Andrade PB, Kim SS, Ahmad W, Leal SM.

Clin Genet. 2013 Sep;84(3):294-6. doi: 10.1111/cge.12047. Epub 2012 Nov 23. No abstract available.

PubMed [citation]

PMID:: 23173898
PMCID:: PMC6220893

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 OMIM, SCV000119869.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 4 patients from 2 unrelated consanguineous Pakistani families with DFNB22 (607039), Lee et al. (2013) identified a homozygous c.1879C-T transition in the OTOA gene, resulting in a pro627-to-ser (P627S) substitution at a highly conserved residue within an exposed coil region as a domain linker. The mutation, which was found by linkage analysis followed by candidate gene sequencing, was not present in 670 control chromosomes. Functional studies of the variant were not performed, but the mutation was predicted to interrupt the superhelical structure of OTOA. The patients had prelingual onset of severe to profound hearing loss affecting all frequencies.

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

From Payam Genetics Center, General Welfare Department of North Khorasan Province, SCV003918902.1

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

Description

The OTOA c.1879C>T (p.Pro627Ser) is a missens mutation and results at the protein level is a disfunctional or truncated protein, predicted lead to disease.This variant is not present in Iranian population databases. This variant as Pathogenic according to the ACMG classification.

#	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		1	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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