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NM_000503.6(EYA1):c.1276G>A (p.Gly426Ser) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 25, 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:
RCV000606853.4

Allele description [Variation Report for NM_000503.6(EYA1):c.1276G>A (p.Gly426Ser)]

NM_000503.6(EYA1):c.1276G>A (p.Gly426Ser)

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.1276G>A (p.Gly426Ser)
Other names:
G393S
HGVS:
  • NC_000008.11:g.71216776C>T
  • NG_011735.3:g.336355G>A
  • NM_000503.6:c.1276G>AMANE SELECT
  • NM_001288574.2:c.1258G>A
  • NM_001288575.2:c.910G>A
  • NM_001370333.1:c.1363G>A
  • NM_001370334.1:c.1276G>A
  • NM_001370335.1:c.1276G>A
  • NM_001370336.1:c.1255G>A
  • NM_172058.4:c.1276G>A
  • NM_172059.5:c.1258G>A
  • NP_000494.2:p.Gly426Ser
  • NP_001275503.1:p.Gly420Ser
  • NP_001275504.1:p.Gly304Ser
  • NP_001357262.1:p.Gly455Ser
  • NP_001357263.1:p.Gly426Ser
  • NP_001357264.1:p.Gly426Ser
  • NP_001357265.1:p.Gly419Ser
  • NP_742055.1:p.Gly426Ser
  • NP_742056.2:p.Gly420Ser
  • NC_000008.10:g.72129011C>T
  • NG_011735.2:g.150457G>A
  • NM_000503.4:c.1276G>A
  • NM_000503.5:c.1276G>A
  • NM_172058.2:c.1276G>A
  • Q99502:p.Gly426Ser
Protein change:
G304S; GLY393SER
Links:
UniProtKB: Q99502#VAR_016865; OMIM: 601653.0010; dbSNP: rs121909199
NCBI 1000 Genomes Browser:
rs121909199
Molecular consequence:
  • NM_000503.6:c.1276G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001288574.2:c.1258G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001288575.2:c.910G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370333.1:c.1363G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370334.1:c.1276G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370335.1:c.1276G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370336.1:c.1255G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172058.4:c.1276G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172059.5:c.1258G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
unknown functional consequence
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000731974Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Uncertain significance
(Sep 25, 2017) 		germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

EYA1 mutations associated with the branchio-oto-renal syndrome result in defective otic development in Xenopus laevis.

Li Y, Manaligod JM, Weeks DL.

Biol Cell. 2010 Feb 17;102(5):277-92. doi: 10.1042/BC20090098.

PubMed [citation]
PMID:
19951260
PMCID:
PMC2825735

Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome.

Patrick AN, Cabrera JH, Smith AL, Chen XS, Ford HL, Zhao R.

Nat Struct Mol Biol. 2013 Apr;20(4):447-53. doi: 10.1038/nsmb.2505. Epub 2013 Feb 24.

PubMed [citation]
PMID:
23435380
PMCID:
PMC3618615
See all PubMed Citations (10)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000731974.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (10)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gly426Ser (c.1276G>A) variant in EYA1 has been reported in one Japanese individual with c onductive hearing loss with additional clinical features of branchio-oto-renal s yndrome (Azuma 2000), and parental testing confirmed de novo occurrence of the v ariant in the individual. This variant has also been identified in 0.18% (33/188 60) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http:/ /gnomad.broadinstitute.org; dbSNP rs121909199); however this frequency is not hi gh enough to rule out a pathogenic role. The variant is also listed in ClinVar ( Variant ID 22977). Computational prediction tools and conservation analysis sugg est the variant may impact the protein. However, several in vitro functional stu dies provide conflicting data on the impact of the variant to normal protein fun ction (Buller 2001, Mutsuddi 2005, Rayapureddi 2006, Zou 2008, Li 2010, Ahmed 20 12, Patrick 2013, Musharraf 2014). It should be noted that in vitro studies may not accurately reflect biological function. In summary, while there is some sus picion for a pathogenic role, the clinical significance of the p.Gly426Ser varia nt is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Oct 8, 2024