NM_000503.6(EYA1):c.1259del (p.Leu420fs) AND Branchiootorenal syndrome 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 28, 2018
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:: RCV001251477.3

Allele description [Variation Report for NM_000503.6(EYA1):c.1259del (p.Leu420fs)]

NM_000503.6(EYA1):c.1259del (p.Leu420fs)

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.1259del (p.Leu420fs)

HGVS:

NC_000008.11:g.71216795del
NG_011735.2:g.150440del
NG_011735.3:g.336338del
NM_000503.6:c.1259delMANE SELECT
NM_001288574.2:c.1241del
NM_001288575.2:c.893del
NM_001370333.1:c.1346del
NM_001370334.1:c.1259del
NM_001370335.1:c.1259del
NM_001370336.1:c.1238del
NM_172058.4:c.1259del
NM_172059.5:c.1241del
NP_000494.2:p.Leu420fs
NP_001275503.1:p.Leu414fs
NP_001275504.1:p.Leu298fs
NP_001357262.1:p.Leu449fs
NP_001357263.1:p.Leu420fs
NP_001357264.1:p.Leu420fs
NP_001357265.1:p.Leu413fs
NP_742055.1:p.Leu420fs
NP_742056.2:p.Leu414fs
NC_000008.10:g.72129030del
NM_000503.4:c.1259delT

Protein change:

L298fs

Links:

dbSNP: rs1809266780

NCBI 1000 Genomes Browser:

rs1809266780

Molecular consequence:

NM_000503.6:c.1259del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001288574.2:c.1241del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001288575.2:c.893del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370333.1:c.1346del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370334.1:c.1259del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370335.1:c.1259del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001370336.1:c.1238del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172058.4:c.1259del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172059.5:c.1241del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Branchiootorenal syndrome 1
Identifiers:: MONDO: MONDO:0007236; MedGen: C4551702; Orphanet: 107; OMIM: 113650

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001427104	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 28, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001427104

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 28, 2018)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV001427104.2

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

Description

A heterozygous frameshift deletion variant, NM_000503.4(EYA1):c.1259delT, has been identified in exon 14 of 18 of the EYA1 gene. This deletion is predicted to create a frameshift starting at amino acid position 420, introducing a stop codon 12 residues downstream, NP_000494.2(EYA1):p.(Leu420Trpfs*12). This variant is predicted to result in loss of protein function either through truncation (a third of the protein) or nonsense-mediated decay. The variant is absent in population databases (gnomAD, dbSNP, 1000G) and has not been previously reported in clinical cases. However, other truncating variants downstream of this variant have been reported as pathogenic in individuals with Branchiootorenal syndrome (ClinVar). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.

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

Last Updated: Nov 5, 2022

ClinVar

Relating variation to medicine