NM_014249.4(NR2E3):c.767C>A (p.Ala256Glu) AND Goldmann-Favre syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 4, 2020
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:: RCV001449815.4

Allele description [Variation Report for NM_014249.4(NR2E3):c.767C>A (p.Ala256Glu)]

NM_014249.4(NR2E3):c.767C>A (p.Ala256Glu)

Gene:

NR2E3:nuclear receptor subfamily 2 group E member 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q23

Genomic location:

Preferred name:

NM_014249.4(NR2E3):c.767C>A (p.Ala256Glu)

HGVS:

NC_000015.10:g.71813408C>A
NG_009113.2:g.7854C>A
NM_014249.4:c.767C>AMANE SELECT
NM_016346.4:c.767C>A
NP_055064.1:p.Ala256Glu
NP_057430.1:p.Ala256Glu
NC_000015.9:g.72105748C>A
NM_014249.2:c.767C>A
NM_014249.3:c.767C>A
NM_016346.3:c.767C>A

Protein change:

A256E

Links:

dbSNP: rs377257254

NCBI 1000 Genomes Browser:

rs377257254

Molecular consequence:

NM_014249.4:c.767C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016346.4:c.767C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Goldmann-Favre syndrome
Identifiers:: MONDO: MONDO:0100289; MedGen: C0339541

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001653112	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Jun 4, 2020)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 19898638, 25097241, 28041643, 29343940, 25703721, 12963616, 25079116, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001653112

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Jun 4, 2020)

germline

clinical testing

PubMed (8)
[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	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A comprehensive analysis of sequence variants and putative disease-causing mutations in photoreceptor-specific nuclear receptor NR2E3.

Kanda A, Swaroop A.

Mol Vis. 2009 Oct 24;15:2174-84.

PubMed [citation]

PMID:: 19898638
PMCID:: PMC2773741

Dependable and efficient clinical utility of target capture-based deep sequencing in molecular diagnosis of retinitis pigmentosa.

Wang J, Zhang VW, Feng Y, Tian X, Li FY, Truong C, Wang G, Chiang PW, Lewis RA, Wong LJ.

Invest Ophthalmol Vis Sci. 2014 Aug 5;55(10):6213-23. doi: 10.1167/iovs.14-14936.

PubMed [citation]

PMID:: 25097241

See all PubMed Citations (8)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV001653112.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (8)

Description

The p.Ala256Glu variant in NR2E3 has been reported in the compound heterozygous state 6 individuals with retinal disease (Sharon 2003 PMID:12963616, Hull 2014 PMID:25079116, Carss 2017 PMID: 28041643, Bryant 2018 PMID: 29343940). It has also been identified in 0.009% (3/34014) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org) and is reported in ClinVar (Variation ID:438229). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro functional studies support an impact on protein function (Kanda 2009 PMID: 19898638, von Alpen 2015 PMID: 25703721). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Enhanced S-Cone syndrome. ACMG/AMP Criteria applied: PM3_VeryStrong, PM2, PS3_Moderate, PP3.

#	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		1	not provided	1	not provided

Last Updated: Oct 8, 2024

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