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NM_144672.4(OTOA):c.1765del (p.Gln589fs) AND Rare genetic deafness

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 22, 2019
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:
RCV001195540.5

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:
1

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001365921Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(May 22, 2019) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown11not providednot providednot providedclinical testing

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

Clarification of glycosylphosphatidylinositol anchorage of OTOANCORIN and human OTOA variants associated with deafness.

Kim BJ, Kim DK, Han JH, Oh J, Kim AR, Lee C, Kim NK, Park HR, Kim MY, Lee S, Lee S, Oh DY, Park WY, Park S, Choi BY.

Hum Mutat. 2019 May;40(5):525-531. doi: 10.1002/humu.23719. Epub 2019 Feb 28.

PubMed [citation]
PMID:
30740825
PMCID:
PMC6467692
See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV001365921.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The p.Gln589ArgfsX55 variant in OTOA has been previously reported in two Korean individuals with hearing loss, one of whom had congenital moderate to severe sensorineural hearing loss and harbored another OTOA variant in trans (Kim 2019, Park 2014). This variant has been identified in 0.01% (3/18394) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 589 and leads to a premature termination codon 55 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the OTOA gene is an established disease mechanism in autosomal recessive nonsyndromic hearing loss. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive hearing loss. ACMG/AMP criteria applied: PVS1, PM3, PM2_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not provided1not provided

Last Updated: Sep 29, 2024