NM_000503.6(EYA1):c.880C>T (p.Arg294Ter) AND Melnick-Fraser syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 14, 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:: RCV001035542.7

Allele description [Variation Report for NM_000503.6(EYA1):c.880C>T (p.Arg294Ter)]

NM_000503.6(EYA1):c.880C>T (p.Arg294Ter)

Gene:

EYA1:EYA transcriptional coactivator and phosphatase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q13.3

Genomic location:

Preferred name:

NM_000503.6(EYA1):c.880C>T (p.Arg294Ter)

HGVS:

NC_000008.11:g.71271844G>A
NG_011735.3:g.281287C>T
NM_000503.6:c.880C>TMANE SELECT
NM_001288574.2:c.862C>T
NM_001288575.2:c.514C>T
NM_001370333.1:c.967C>T
NM_001370334.1:c.880C>T
NM_001370335.1:c.880C>T
NM_001370336.1:c.949C>T
NM_172058.4:c.880C>T
NM_172059.5:c.952C>T
NP_000494.2:p.Arg294Ter
NP_001275503.1:p.Arg288Ter
NP_001275504.1:p.Arg172Ter
NP_001357262.1:p.Arg323Ter
NP_001357263.1:p.Arg294Ter
NP_001357264.1:p.Arg294Ter
NP_001357265.1:p.Arg317Ter
NP_742055.1:p.Arg294Ter
NP_742056.2:p.Arg318Ter
NC_000008.10:g.72184079G>A
NG_011735.2:g.95389C>T
NM_000503.4:c.880C>T
NM_000503.5:c.880C>T

Protein change:

R172*

Links:

dbSNP: rs1816578250

NCBI 1000 Genomes Browser:

rs1816578250

Molecular consequence:

NM_000503.6:c.880C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001288574.2:c.862C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001288575.2:c.514C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370333.1:c.967C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370334.1:c.880C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370335.1:c.880C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001370336.1:c.949C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_172058.4:c.880C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_172059.5:c.952C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Melnick-Fraser syndrome (BOR1)
Synonyms:: Branchio-oto-renal syndrome; Branchiootorenal syndrome
Identifiers:: MONDO: MONDO:0007029; MedGen: C0265234

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001198871	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 14, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9603436, 21280147, 10464653, 18220287, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001198871

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 14, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of three novel mutations in human EYA1 protein associated with branchio-oto-renal syndrome.

Kumar S, Kimberling WJ, Weston MD, Schaefer BG, Berg MA, Marres HA, Cremers CW.

Hum Mutat. 1998;11(6):443-9.

PubMed [citation]

PMID:: 9603436

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, Morinière V, Marlin S, Koubi V, Gabriel HD, Colin E, Bonneau D, Salomon R, Antignac C, Heidet L.

Hum Mutat. 2011 Feb;32(2):183-90. doi: 10.1002/humu.21402.

PubMed [citation]

PMID:: 21280147

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001198871.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

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).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 30, 2024

ClinVar

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