NM_001142800.2(EYS):c.8648_8655del (p.Thr2883fs) AND Retinitis pigmentosa 25

Germline classification:: Pathogenic/Likely pathogenic (7 submissions)
Last evaluated:: Oct 22, 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:: RCV000664636.11

Allele description [Variation Report for NM_001142800.2(EYS):c.8648_8655del (p.Thr2883fs)]

NM_001142800.2(EYS):c.8648_8655del (p.Thr2883fs)

Genes:

PHF3:PHD finger protein 3 [Gene - OMIM - HGNC]
EYS:eyes shut homolog [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

6q12

Genomic location:

Preferred name:

NM_001142800.2(EYS):c.8648_8655del (p.Thr2883fs)

HGVS:

NC_000006.12:g.63721377_63721384del
NG_023443.2:g.1990843_1990850del
NM_001142800.2:c.8648_8655delMANE SELECT
NM_001290259.2:c.*7669_*7676del
NM_001292009.2:c.8711_8718del
NM_001370348.2:c.*7669_*7676delMANE SELECT
NM_001370349.2:c.*7669_*7676del
NM_001370350.2:c.*7669_*7676del
NM_015153.4:c.*7669_*7676del
NP_001136272.1:p.Thr2883fs
NP_001278938.1:p.Thr2904fs
FM209056.1:c.8711_8718delCATGCAGA
NC_000006.11:g.64431272_64431279del
NC_000006.11:g.64431273_64431280del
NM_001142800.1:c.8648_8655del8
NM_001142800.1:c.8648_8655delCATGCAGA

Protein change:

T2883fs

Links:

dbSNP: rs528919874

NCBI 1000 Genomes Browser:

rs528919874

Molecular consequence:

NM_001290259.2:c.*7669_*7676del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001370348.2:c.*7669_*7676del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001370349.2:c.*7669_*7676del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001370350.2:c.*7669_*7676del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_015153.4:c.*7669_*7676del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001142800.2:c.8648_8655del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001292009.2:c.8711_8718del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Retinitis pigmentosa 25 (RP25)
Synonyms:: RP 25
Identifiers:: MONDO: MONDO:0011272; MedGen: C1864446; Orphanet: 791; OMIM: 602772

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000788634	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Dec 29, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001142361	Reproductive Health Research and Development, BGI Genomics	no assertion criteria provided	Pathogenic (Jan 6, 2020)	germline	curation
SCV001573433	Ocular Genomics Institute, Massachusetts Eye and Ear	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 8, 2021)	germline	research	PubMed (4) [See all records that cite these PMIDs] 30718709, 22363543, 20537394, 25741868
SCV002083481	Natera, Inc.	no assertion criteria provided	Pathogenic (Aug 23, 2021)	germline	clinical testing
SCV002579229	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 2, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004192871	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 22, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004235273	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 22, 2023)	germline	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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing, research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.

Jespersgaard C, Fang M, Bertelsen M, Dang X, Jensen H, Chen Y, Bech N, Dai L, Rosenberg T, Zhang J, Møller LB, Tümer Z, Brøndum-Nielsen K, Grønskov K.

Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.

PubMed [citation]

PMID:: 30718709
PMCID:: PMC6362094

Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population.

Hosono K, Ishigami C, Takahashi M, Park DH, Hirami Y, Nakanishi H, Ueno S, Yokoi T, Hikoya A, Fujita T, Zhao Y, Nishina S, Shin JP, Kim IT, Yamamoto S, Azuma N, Terasaki H, Sato M, Kondo M, Minoshima S, Hotta Y.

PLoS One. 2012;7(2):e31036. doi: 10.1371/journal.pone.0031036. Epub 2012 Feb 17.

PubMed [citation]

PMID:: 22363543
PMCID:: PMC3281914

See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000788634.1

#	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

From Reproductive Health Research and Development, BGI Genomics, SCV001142361.1

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

Description

NM_001142800.1:c.8648_8655delCATGCAGA in the EYS gene has an allele frequency of 0.006 in European (Finnish) subpopulation in the gnomAD database. This sequence change results in a premature translational stop signal in the EYS gene (p.Thr2883Lysfs*4). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 262 amino acids of the EYS protein. This variant has been observed in a patient with retinitis pigmentosa, in a compound heterozygous state with c.4350_4356del7 (p.K1450KfsX3) (PMID: 20537394). This variant is also known as c.8710_8717del8 (p.T2904KfsX4) in the literature. Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PVS1; PM3; PP4.

#	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

From Ocular Genomics Institute, Massachusetts Eye and Ear, SCV001573433.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (4)

Description

The EYS c.8648_8655del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3. Based on this evidence we have classified this variant as Pathogenic.

#	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 Natera, Inc., SCV002083481.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From MGZ Medical Genetics Center, SCV002579229.1

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

From Baylor Genetics, SCV004192871.1

#	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

From Revvity Omics, Revvity, SCV004235273.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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