ClinVar Genomic variation as it relates to human health
NM_000503.6(EYA1):c.880C>T (p.Arg294Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000503.6(EYA1):c.880C>T (p.Arg294Ter)
Variation ID: 834788 Accession: VCV000834788.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8q13.3 8: 72184079 (GRCh37) [ NCBI UCSC ] 8: 71271844 (GRCh38) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 15, 2020 Feb 14, 2024 Aug 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000503.6:c.880C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000494.2:p.Arg294Ter nonsense NM_001288574.2:c.862C>T NP_001275503.1:p.Arg288Ter nonsense NM_001288575.2:c.514C>T NP_001275504.1:p.Arg172Ter nonsense NM_001370333.1:c.967C>T NP_001357262.1:p.Arg323Ter nonsense NM_001370334.1:c.880C>T NP_001357263.1:p.Arg294Ter nonsense NM_001370335.1:c.880C>T NP_001357264.1:p.Arg294Ter nonsense NM_001370336.1:c.949C>T NP_001357265.1:p.Arg317Ter nonsense NM_172058.4:c.880C>T NP_742055.1:p.Arg294Ter nonsense NM_172059.5:c.952C>T NP_742056.2:p.Arg318Ter nonsense NC_000008.11:g.71271844G>A NC_000008.10:g.72184079G>A NG_011735.3:g.281287C>T - Protein change
- R172*, R318*, R317*, R323*, R288*, R294*
- Other names
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- Canonical SPDI
- NC_000008.11:71271843:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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EYA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
518 | 556 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Oct 14, 2022 | RCV001035542.7 | |
Pathogenic (3) |
criteria provided, single submitter
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Nov 4, 2021 | RCV001569637.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 14, 2022 | RCV002552091.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 8, 2023 | RCV003336276.3 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Dec 14, 2022)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003663941.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
The c.880C>T (p.R294*) alteration, located in exon 10 (coding exon 8) of the EYA1 gene, consists of a C to T substitution at nucleotide position … (more)
The c.880C>T (p.R294*) alteration, located in exon 10 (coding exon 8) of the EYA1 gene, consists of a C to T substitution at nucleotide position 880. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 294. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration was detected in multiple individuals with branchio-oto-renal syndrome (Kumar, 1998; Krug, 2011; Unzaki, 2018). This variant was also determined to be the result of a de novo mutation or germline mosaicism in one individual from a cohort of patients with hearing loss (Wu, 2022). Based on the available evidence, this alteration is classified as pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(Nov 04, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001793756.3
First in ClinVar: Aug 21, 2021 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9603436, 25525159, 18220287, 21280147) (less)
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Pathogenic
(Aug 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Branchiootorenal syndrome 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV004045935.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Preauricular pit (present) , Unilateral renal agenesis (present) , Conductive hearing impairment (present) , Cleft palate (present) , Abnormality of the outer ear (present) , … (more)
Preauricular pit (present) , Unilateral renal agenesis (present) , Conductive hearing impairment (present) , Cleft palate (present) , Abnormality of the outer ear (present) , Sensorineural hearing loss disorder (present) (less)
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Pathogenic
(Oct 14, 2022)
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criteria provided, single submitter
Method: clinical testing
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Melnick-Fraser syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001198871.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 834788). This variant is also known … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 834788). This variant is also known as c.781C>T (p.Arg261X). This premature translational stop signal has been observed in individuals with clinical features of Branchio-oto-renal syndrome (PMID: 9603436, 21280147). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg294*) in the EYA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EYA1 are known to be pathogenic (PMID: 10464653, 18220287). (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001809265.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001952164.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Molecular diagnose of a large hearing loss population from China by targeted genome sequencing. | Wu J | Journal of human genetics | 2022 | PMID: 35982127 |
Clinically diverse phenotypes and genotypes of patients with branchio-oto-renal syndrome. | Unzaki A | Journal of human genetics | 2018 | PMID: 29500469 |
Mutation screening of the EYA1, SIX1, and SIX5 genes in a large cohort of patients harboring branchio-oto-renal syndrome calls into question the pathogenic role of SIX5 mutations. | Krug P | Human mutation | 2011 | PMID: 21280147 |
Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR. | Orten DJ | Human mutation | 2008 | PMID: 18220287 |
Identification of three novel mutations in human EYA1 protein associated with branchio-oto-renal syndrome. | Kumar S | Human mutation | 1998 | PMID: 9603436 |
Branchio-oto-renal syndrome: identification of novel mutations, molecular characterization, mutation distribution, and prospects for genetic testing. | Kumar S | Genetic testing | 1997 | PMID: 10464653 |
Text-mined citations for rs1816578250 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.