ClinVar Genomic variation as it relates to human health
NM_000503.6(EYA1):c.1081C>T (p.Arg361Ter)
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.1081C>T (p.Arg361Ter)
Variation ID: 7943 Accession: VCV000007943.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8q13.3 8: 71244662 (GRCh38) [ NCBI UCSC ] 8: 72156897 (GRCh37) [ 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 4, 2013 Oct 8, 2024 Mar 5, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000503.6:c.1081C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000494.2:p.Arg361Ter nonsense NM_000503.4:c.1081C>T NM_001288574.2:c.1063C>T NP_001275503.1:p.Arg355Ter nonsense NM_001288575.2:c.715C>T NP_001275504.1:p.Arg239Ter nonsense NM_001370333.1:c.1168C>T NP_001357262.1:p.Arg390Ter nonsense NM_001370334.1:c.1081C>T NP_001357263.1:p.Arg361Ter nonsense NM_001370335.1:c.1081C>T NP_001357264.1:p.Arg361Ter nonsense NM_001370336.1:c.1119+25078C>T intron variant NM_172058.3:c.1081C>T NM_172058.4:c.1081C>T NP_742055.1:p.Arg361Ter nonsense NM_172059.5:c.1122+25078C>T intron variant NC_000008.11:g.71244662G>A NC_000008.10:g.72156897G>A NG_011735.3:g.308469C>T - Protein change
- R361*, R355*, R239*, R390*
- Other names
- R328*
- Canonical SPDI
- NC_000008.11:71244661: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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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 |
544 | 582 |
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 (2) |
criteria provided, single submitter
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Jan 5, 2022 | RCV000008406.8 | |
Pathogenic (1) |
no assertion criteria provided
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Mar 1, 2008 | RCV000008405.4 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 21, 2022 | RCV001823094.18 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 28, 2021 | RCV002512905.3 | |
EYA1-related disorder
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Pathogenic (2) |
criteria provided, single submitter
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Mar 5, 2024 | RCV004554585.2 |
Pathogenic (1) |
criteria provided, single submitter
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Aug 22, 2023 | RCV002228020.5 |
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
Help
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
Help
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
(Apr 28, 2021)
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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: SCV003564599.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.1081C>T (p.R361*) alteration, located in exon 12 (coding exon 10) of the EYA1 gene, consists of a C to T substitution at nucleotide position … (more)
The c.1081C>T (p.R361*) alteration, located in exon 12 (coding exon 10) of the EYA1 gene, consists of a C to T substitution at nucleotide position 1081. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 361. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. The EYA1 c.1081C>T alteration was flagged as a low confidence call in the Genome Aggregation Database (gnomAD). This alteration has been reported in multiple patients with branchio-oto-renal (BOR) syndrome (Krug, 2011; Olavarrieta, 2008; Orten, 2008; Sloan-Heggen, 2016). Based on the available evidence, this alteration is classified as pathogenic. (less)
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Pathogenic
(Jan 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Branchiootorenal syndrome 1
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002061219.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Comment:
The c.1081C>T;p.(Arg361*) variant creates a premature translational stop signal in EYA1 gene. It is expected to result in an absent or disrupted protein product -PVS1.This … (more)
The c.1081C>T;p.(Arg361*) variant creates a premature translational stop signal in EYA1 gene. It is expected to result in an absent or disrupted protein product -PVS1.This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 7943; PMID: 26969326;18177466; 21280147) - PS4. This variant is not present in population databases (rs121909202, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Uruguay
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Pathogenic
(Aug 22, 2023)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000630898.5
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 7943). This variant is also known as Arg328X. This premature translational stop signal has been observed … (more)
ClinVar contains an entry for this variant (Variation ID: 7943). This variant is also known as Arg328X. This premature translational stop signal has been observed in individual(s) with branchio-oto-renal syndrome (PMID: 16691597, 18177466, 21280147, 26969326). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg361*) 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). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Sep 21, 2022)
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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: SCV002072826.3
First in ClinVar: Feb 04, 2022 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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 18177466, 25525159, 26969326, 34387732, 31581539, 21280147, 16691597) (less)
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Pathogenic
(Mar 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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EYA1-related disorder
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV005043896.1
First in ClinVar: May 19, 2024 Last updated: May 19, 2024 |
Comment:
PVS1, PS4, PM2
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Pathogenic
(Jun 01, 2022)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002545623.15
First in ClinVar: Jul 09, 2022 Last updated: Oct 08, 2024 |
Number of individuals with the variant: 2
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Pathogenic
(Mar 01, 2008)
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no assertion criteria provided
Method: literature only
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BRANCHIOOTIC SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000028613.2
First in ClinVar: Apr 04, 2013 Last updated: Sep 22, 2019 |
Comment on evidence:
In an infant with a variant form of branchiootic syndrome (BOS1; 602588), Spruijt et al. (2006) identified a heterozygous 982C-T transition in exon 10 of … (more)
In an infant with a variant form of branchiootic syndrome (BOS1; 602588), Spruijt et al. (2006) identified a heterozygous 982C-T transition in exon 10 of the EYA1 gene, resulting in an arg328-to-ter (R328X) substitution predicted to lead to a nonfunctional protein. The patient had severe obstructive sleep apnea caused by laryngomalacia, pharyngomalacia, glossoptosis, and tracheobronchomalacia. He also had retrognathia, bilateral branchial fistulae, ear anomalies, including ear pits, simple helices, and slight cup-shaped and low-set left ear. His mother, who also carried the mutation, had mild retrognathia, left-sided branchial neck fistula, left-sided preauricular pit, and right-sided branchial cyst in the neck. Kidney ultrasound and hearing were normal in both the mother and son. The findings expanded the phenotypic anomalies of BO syndrome associated with EYA1 mutations. Olavarrieta et al. (2008) identified a de novo R328X mutation in the EYA1 gene in a Spanish man with branchiootorenal syndrome (BOR1; 113650). He had branchial fistulae, preauricular pits, renal agenesis, and mixed hearing loss. In addition, he had myopia, vitreous anomaly, flat face, and cleft palate, characteristic of Stickler syndrome type I (STL1; 108300) and was found to also carry a mutation in the COL2A1 gene (120140). Olavarrieta et al. (2008) emphasized that both disorders show phenotypic variability as well as overlapping features, which can complicate a precise diagnosis. Thorough clinical evaluation is necessary to identify coexisting genetic syndromes in the same patient. (less)
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Pathogenic
(Mar 01, 2008)
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no assertion criteria provided
Method: literature only
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BRANCHIOOTORENAL SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000028614.2
First in ClinVar: Apr 04, 2013 Last updated: Sep 22, 2019 |
Comment on evidence:
In an infant with a variant form of branchiootic syndrome (BOS1; 602588), Spruijt et al. (2006) identified a heterozygous 982C-T transition in exon 10 of … (more)
In an infant with a variant form of branchiootic syndrome (BOS1; 602588), Spruijt et al. (2006) identified a heterozygous 982C-T transition in exon 10 of the EYA1 gene, resulting in an arg328-to-ter (R328X) substitution predicted to lead to a nonfunctional protein. The patient had severe obstructive sleep apnea caused by laryngomalacia, pharyngomalacia, glossoptosis, and tracheobronchomalacia. He also had retrognathia, bilateral branchial fistulae, ear anomalies, including ear pits, simple helices, and slight cup-shaped and low-set left ear. His mother, who also carried the mutation, had mild retrognathia, left-sided branchial neck fistula, left-sided preauricular pit, and right-sided branchial cyst in the neck. Kidney ultrasound and hearing were normal in both the mother and son. The findings expanded the phenotypic anomalies of BO syndrome associated with EYA1 mutations. Olavarrieta et al. (2008) identified a de novo R328X mutation in the EYA1 gene in a Spanish man with branchiootorenal syndrome (BOR1; 113650). He had branchial fistulae, preauricular pits, renal agenesis, and mixed hearing loss. In addition, he had myopia, vitreous anomaly, flat face, and cleft palate, characteristic of Stickler syndrome type I (STL1; 108300) and was found to also carry a mutation in the COL2A1 gene (120140). Olavarrieta et al. (2008) emphasized that both disorders show phenotypic variability as well as overlapping features, which can complicate a precise diagnosis. Thorough clinical evaluation is necessary to identify coexisting genetic syndromes in the same patient. (less)
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Pathogenic
(Mar 11, 2024)
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no assertion criteria provided
Method: clinical testing
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EYA1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV005348476.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The EYA1 c.1081C>T variant is predicted to result in premature protein termination (p.Arg361*). This variant is alternatively referred to as c.982C>T in the literature. This … (more)
The EYA1 c.1081C>T variant is predicted to result in premature protein termination (p.Arg361*). This variant is alternatively referred to as c.982C>T in the literature. This variant has been reported in individuals with branchiootorenal syndrome, and in some cases was determined to be de novo (Spruijt et al. 2006. PubMed ID: 16691597; Sloan-Heggen et al. 2016. PubMed ID: 26969326; Orten et al. 2008. PubMed ID: 18220287; Fu et al. 2022. PubMed ID: 36307859). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in EYA1 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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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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Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. | Sloan-Heggen CM | Human genetics | 2016 | PMID: 26969326 |
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 |
Stickler and branchio-oto-renal syndromes in a patient with mutations in EYA1 and COL2A1 genes. | Olavarrieta L | Clinical genetics | 2008 | PMID: 18177466 |
Identification of a novel EYA1 mutation presenting in a newborn with laryngomalacia, glossoptosis, retrognathia, and pectus excavatum. | Spruijt L | American journal of medical genetics. Part A | 2006 | PMID: 16691597 |
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 rs121909202 ...
HelpRecord last updated Oct 08, 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.