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NM_016239.4(MYO15A):c.6337A>T (p.Ile2113Phe) AND Nonsyndromic genetic hearing loss

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 17, 2024
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV002228014.2

Allele description [Variation Report for NM_016239.4(MYO15A):c.6337A>T (p.Ile2113Phe)]

NM_016239.4(MYO15A):c.6337A>T (p.Ile2113Phe)

Gene:
MYO15A:myosin XVA [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_016239.4(MYO15A):c.6337A>T (p.Ile2113Phe)
Other names:
I892F; NM_016239.4(MYO15A):c.6337A>T
HGVS:
  • NC_000017.11:g.18145935A>T
  • NG_011634.2:g.42230A>T
  • NM_016239.4:c.6337A>TMANE SELECT
  • NP_057323.3:p.Ile2113Phe
  • NC_000017.10:g.18049249A>T
  • NC_000017.10:g.18049249A>T
  • NG_011634.1:g.42230A>T
  • Q9UKN7:p.Ile2113Phe
Protein change:
I2113F; ILE892PHE
Links:
UniProtKB: Q9UKN7#VAR_010304; OMIM: 602666.0001; dbSNP: rs121908965
NCBI 1000 Genomes Browser:
rs121908965
Molecular consequence:
  • NM_016239.4:c.6337A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Nonsyndromic genetic hearing loss
Synonyms:
Nonsyndromic hearing loss and deafness; Non-syndromic genetic deafness; Nonsyndromic genetic deafness
Identifiers:
MONDO: MONDO:0019497; MedGen: C5680182; Orphanet: 87884

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002512128ClinGen Hearing Loss Variant Curation Expert Panel
reviewed by expert panel

(clingen hl acmg specifications otof myo15a v1)		Likely Pathogenic
(Jul 17, 2024) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Hearing Loss Variant Curation Expert Panel, SCV002512128.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.6337A>T is a missense variant in MYO15A predicted to cause a substitution of isoleucine to phenylalanine at amino acid 2113. This variant is absent in gnomAD v4.1 (PM2_Supporting). However, it has been described as a founder variant with a carrier frequency of 25/100 in Bengkala, Bali (PMID: 9603736). This variant has been identified in the homozygous state in 1 Bengkala kindred with hearing loss and in the heterozygous state in one Chinese individual with hearing loss (PMIDs: 9603736, 27018975). The p.Ile2113Phe variant has been reported to segregate with hearing loss in at least 6 family members (PP1_Strong; PMID: 9603736). The REVEL computational prediction analysis tool produced a score of 0.91, which is above the threshold necessary to apply PP3 (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive hearing loss based on the ACMG/AMP criteria applied as specified by the ClinGen Hearing Loss VCEP: PP1_Strong, PP3, PM2_Supporting. (The ClinGen Hearing Loss VCEP Specifications Version 1, 07/17/2024)

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

Last Updated: Oct 13, 2024