NM_000503.6(EYA1):c.1236dup (p.Ala413fs) AND Melnick-Fraser syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 30, 2021
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:: RCV001956351.4

Allele description [Variation Report for NM_000503.6(EYA1):c.1236dup (p.Ala413fs)]

NM_000503.6(EYA1):c.1236dup (p.Ala413fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

8q13.3

Genomic location:

Preferred name:

NM_000503.6(EYA1):c.1236dup (p.Ala413fs)

HGVS:

NC_000008.11:g.71216816dup
NG_011735.3:g.336315dup
NM_000503.6:c.1236dupMANE SELECT
NM_001288574.2:c.1218dup
NM_001288575.2:c.870dup
NM_001370333.1:c.1323dup
NM_001370334.1:c.1236dup
NM_001370335.1:c.1236dup
NM_001370336.1:c.1215dup
NM_172058.4:c.1236dup
NM_172059.5:c.1218dup
NP_000494.2:p.Ala413fs
NP_001275503.1:p.Ala407fs
NP_001275504.1:p.Ala291fs
NP_001357262.1:p.Ala442fs
NP_001357263.1:p.Ala413fs
NP_001357264.1:p.Ala413fs
NP_001357265.1:p.Ala406fs
NP_742055.1:p.Ala413fs
NP_742056.2:p.Ala407fs
NC_000008.10:g.72129050_72129051insT
NC_000008.10:g.72129051dup

Protein change:

A291fs

Links:

dbSNP: rs2128854105

NCBI 1000 Genomes Browser:

rs2128854105

Molecular consequence:

NM_000503.6:c.1236dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001288574.2:c.1218dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001288575.2:c.870dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370333.1:c.1323dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370334.1:c.1236dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370335.1:c.1236dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370336.1:c.1215dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172058.4:c.1236dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172059.5:c.1218dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Melnick-Fraser syndrome (BOR)
Synonyms:: Branchio-oto-renal syndrome; Branchiootorenal syndrome
Identifiers:: MONDO: MONDO:0007029; MedGen: C0265234; OMIM: PS113650

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002243789	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 30, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10464653, 18220287, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002243789

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 30, 2021)

germline

clinical testing

PubMed (3)
[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

Branchio-oto-renal syndrome: identification of novel mutations, molecular characterization, mutation distribution, and prospects for genetic testing.

Kumar S, Deffenbacher K, Cremers CW, Van Camp G, Kimberling WJ.

Genet Test. 1997-1998;1(4):243-51.

PubMed [citation]

PMID:: 10464653

Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR.

Orten DJ, Fischer SM, Sorensen JL, Radhakrishna U, Cremers CW, Marres HA, Van Camp G, Welch KO, Smith RJ, Kimberling WJ.

Hum Mutat. 2008 Apr;29(4):537-44. doi: 10.1002/humu.20691.

PubMed [citation]

PMID:: 18220287

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002243789.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with EYA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ala413Serfs*5) 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: Sep 29, 2024

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