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NM_004100.5(EYA4):c.1574G>A (p.Trp525Ter) AND Dilated cardiomyopathy 1J

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 15, 2022
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:
RCV003034488.2

Allele description [Variation Report for NM_004100.5(EYA4):c.1574G>A (p.Trp525Ter)]

NM_004100.5(EYA4):c.1574G>A (p.Trp525Ter)

Genes:
EYA4:EYA transcriptional coactivator and phosphatase 4 [Gene - OMIM - HGNC]
TARID:TCF21 antisense RNA inducing promoter demethylation [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q23.2
Genomic location:
Preferred name:
NM_004100.5(EYA4):c.1574G>A (p.Trp525Ter)
HGVS:
  • NC_000006.12:g.133515393G>A
  • NG_011596.2:g.279037G>A
  • NM_001301012.2:c.1412G>A
  • NM_001301013.2:c.1592G>A
  • NM_001370458.1:c.1505G>A
  • NM_001370459.1:c.1430G>A
  • NM_004100.5:c.1574G>AMANE SELECT
  • NM_172103.4:c.1505G>A
  • NM_172105.4:c.1574G>A
  • NP_001287941.1:p.Trp471Ter
  • NP_001287942.1:p.Trp531Ter
  • NP_001357387.1:p.Trp502Ter
  • NP_001357388.1:p.Trp477Ter
  • NP_004091.3:p.Trp525Ter
  • NP_742101.2:p.Trp502Ter
  • NP_742103.1:p.Trp525Ter
  • LRG_418t1:c.1574G>A
  • LRG_418:g.279037G>A
  • LRG_418p1:p.Trp525Ter
  • NC_000006.11:g.133836531G>A
Protein change:
W471*
Molecular consequence:
  • NM_001301012.2:c.1412G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001301013.2:c.1592G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001370458.1:c.1505G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001370459.1:c.1430G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004100.5:c.1574G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_172103.4:c.1505G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_172105.4:c.1574G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Dilated cardiomyopathy 1J (CMD1J)
Synonyms:
CARDIOMYOPATHY, DILATED, WITH SENSORINEURAL HEARING LOSS, AUTOSOMAL DOMINANT
Identifiers:
MONDO: MONDO:0011541; MedGen: C1854368; Orphanet: 217622; OMIM: 605362

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003326800Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Mar 15, 2022) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus.

Wayne S, Robertson NG, DeClau F, Chen N, Verhoeven K, Prasad S, Tranebjärg L, Morton CC, Ryan AF, Van Camp G, Smith RJ.

Hum Mol Genet. 2001 Feb 1;10(3):195-200.

PubMed [citation]
PMID:
11159937

Evaluation of the contribution of the EYA4 and GRHL2 genes in Korean patients with autosomal dominant non-syndromic hearing loss.

Kim YR, Kim MA, Sagong B, Bae SH, Lee HJ, Kim HJ, Choi JY, Lee KY, Kim UK.

PLoS One. 2015;10(3):e0119443. doi: 10.1371/journal.pone.0119443.

PubMed [citation]
PMID:
25781927
PMCID:
PMC4363478
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV003326800.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with EYA4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp525*) in the EYA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EYA4 are known to be pathogenic (PMID: 11159937, 25781927, 25963406).

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

Last Updated: Feb 20, 2024