NM_000503.6(EYA1):c.1013_1016del (p.Ser338fs) AND Melnick-Fraser syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 5, 2017
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:: RCV002233959.11

Allele description [Variation Report for NM_000503.6(EYA1):c.1013_1016del (p.Ser338fs)]

NM_000503.6(EYA1):c.1013_1016del (p.Ser338fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

8q13.3

Genomic location:

Preferred name:

NM_000503.6(EYA1):c.1013_1016del (p.Ser338fs)

HGVS:

NC_000008.10:g.72182009_72182012del
NC_000008.11:g.71269775_71269778del
NG_011735.3:g.283354_283357del
NM_000503.6:c.1013_1016delMANE SELECT
NM_001288574.2:c.995_998del
NM_001288575.2:c.647_650del
NM_001370333.1:c.1100_1103del
NM_001370334.1:c.1013_1016del
NM_001370335.1:c.1013_1016del
NM_001370336.1:c.1082_1085del
NM_172058.4:c.1013_1016del
NM_172059.5:c.1085_1088del
NP_000494.2:p.Ser338fs
NP_001275503.1:p.Ser332fs
NP_001275504.1:p.Ser216fs
NP_001357262.1:p.Ser367fs
NP_001357263.1:p.Ser338fs
NP_001357264.1:p.Ser338fs
NP_001357265.1:p.Ser361fs
NP_742055.1:p.Ser338fs
NP_742056.2:p.Ser362fs
NC_000008.10:g.72182009_72182012del
NC_000008.10:g.72182009_72182012delAAGG
NC_000008.10:g.72182010_72182013del
NG_011735.2:g.97456_97459del
NM_000503.5:c.1013_1016delCCTT

Protein change:

S216fs

Links:

dbSNP: rs1554615536

NCBI 1000 Genomes Browser:

rs1554615536

Molecular consequence:

NM_000503.6:c.1013_1016del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001288574.2:c.995_998del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001288575.2:c.647_650del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370333.1:c.1100_1103del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370334.1:c.1013_1016del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370335.1:c.1013_1016del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370336.1:c.1082_1085del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172058.4:c.1013_1016del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172059.5:c.1085_1088del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000755442	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 5, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18220287, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000755442

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 5, 2017)

germline

clinical testing

PubMed (2)
[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 (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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000755442.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in EYA1 are known to be pathogenic (PMID: 18220287). This variant has not been reported in the literature in individuals with EYA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser338Cysfs*27) in the EYA1 gene. It is expected to result in an absent or disrupted protein product.

#	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: Apr 15, 2024

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