NM_014249.4(NR2E3):c.119-2A>C AND Enhanced S-cone syndrome

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Oct 30, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000005864.14

Allele description [Variation Report for NM_014249.4(NR2E3):c.119-2A>C]

NM_014249.4(NR2E3):c.119-2A>C

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.119-2A>C

Other names:

NP_055064.1:p.?

HGVS:

NC_000015.10:g.71811481A>C
NG_009113.2:g.5927A>C
NM_014249.4:c.119-2A>CMANE SELECT
NM_016346.4:c.119-2A>C
NC_000015.9:g.72103821A>C
NM_014249.2:c.119-2A>C
NM_014249.3:c.119-2A>C
NM_016346.2:c.119-2A>C
NM_016346.3:c.119-2A>C

Nucleotide change:

IVS1AS, A-C

Links:

OMIM: 604485.0001; dbSNP: rs2723341

NCBI 1000 Genomes Browser:

rs2723341

Molecular consequence:

NM_014249.4:c.119-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_016346.4:c.119-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Enhanced S-cone syndrome (ESCS)
Identifiers:: MONDO: MONDO:0100288; MedGen: C1849394; Orphanet: 53540; OMIM: 268100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026046	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2008)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10655056, 18294254
SCV001139647	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001161154	Sharon lab, Hadassah-Hebrew University Medical Center	no assertion criteria provided	Pathogenic (Jun 23, 2019)	inherited	research
SCV001366568	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 19, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001572880	Hadassah Hebrew University Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 20, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004191580	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 30, 2023)	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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate.

Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, Beck G, Hockey R, Hanna DB, Gorman S, Duhl D, Carmi R, Bennett J, Weleber RG, Fishman GA, Wright AF, Stone EM, Sheffield VC.

Nat Genet. 2000 Feb;24(2):127-31.

PubMed [citation]

PMID:: 10655056

Analysis of the involvement of the NR2E3 gene in autosomal recessive retinal dystrophies.

Bernal S, Solans T, Gamundi MJ, Hernan I, de Jorge L, Carballo M, Navarro R, Tizzano E, Ayuso C, Baiget M.

Clin Genet. 2008 Apr;73(4):360-6. doi: 10.1111/j.1399-0004.2008.00963.x. Epub 2008 Feb 20.

PubMed [citation]

PMID:: 18294254

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000026046.4

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

Description

Enhanced S-Cone Syndrome

In 3 affected individuals of an extensive kindred with enhanced S-cone syndrome (ESCS; 268100), Haider et al. (2000) identified homozygosity for a splice acceptor site mutation, an A-to-C transversion in the splice acceptor site of intron 1 of the NR2E3 gene. Another distantly related affected family member was found to be heterozygous for the mutation, which was also identified in 8 simplex probands with ESCS. The mutation was not found in 500 control individuals.

Retinitis Pigmentosa 37

In a brother and sister with retinitis pigmentosa and hypopigmented clumped lesions in the posterior pole of both eyes (RP37; 611131), Bernal et al. (2008) identified homozygosity for the 119-2A-C splice acceptor mutation in intron 1 of the NR2E3 gene. Analysis of the RT-PCR products from the mRNA transcripts generated in transient expression studies showed that the mutation generated an aberrant splicing mechanism. The mutation was not found in 60 blood donor controls.

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

From Mendelics, SCV001139647.1

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

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

From Sharon lab, Hadassah-Hebrew University Medical Center, SCV001161154.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	not provided

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

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001366568.2

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

Description

This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5.

#	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

From Hadassah Hebrew University Medical Center, SCV001572880.1

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

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

From Baylor Genetics, SCV004191580.1

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

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

Last Updated: May 7, 2024

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