NM_001142800.2(EYS):c.6416G>A (p.Cys2139Tyr) AND Retinitis pigmentosa 25

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Mar 30, 2024
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:: RCV001376308.11

Allele description [Variation Report for NM_001142800.2(EYS):c.6416G>A (p.Cys2139Tyr)]

NM_001142800.2(EYS):c.6416G>A (p.Cys2139Tyr)

Gene:

EYS:eyes shut homolog [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q12

Genomic location:

Preferred name:

NM_001142800.2(EYS):c.6416G>A (p.Cys2139Tyr)

HGVS:

NC_000006.12:g.64230600C>T
NG_023443.2:g.1481626G>A
NM_001142800.2:c.6416G>AMANE SELECT
NM_001292009.2:c.6416G>A
NP_001136272.1:p.Cys2139Tyr
NP_001278938.1:p.Cys2139Tyr
NC_000006.11:g.64940493C>T
NM_001142800.1:c.6416G>A
Q5T1H1:p.Cys2139Tyr

Protein change:

C2139Y

Links:

UniProtKB: Q5T1H1#VAR_063478; dbSNP: rs749909863

NCBI 1000 Genomes Browser:

rs749909863

Molecular consequence:

NM_001142800.2:c.6416G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001292009.2:c.6416G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001573403	Ocular Genomics Institute, Massachusetts Eye and Ear	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 8, 2021)	germline	research	PubMed (5) [See all records that cite these PMIDs] 24670872, 20333770, 20237254, 27375351, 25741868
SCV002024540	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 14, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002521640	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20237254, 25366773, 25741868
SCV002580690	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 11, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004192862	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2024)	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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	2	not provided	not provided	1	not provided	clinical testing, research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

SLC7A14 linked to autosomal recessive retinitis pigmentosa.

Jin ZB, Huang XF, Lv JN, Xiang L, Li DQ, Chen J, Huang C, Wu J, Lu F, Qu J.

Nat Commun. 2014 Mar 27;5:3517. doi: 10.1038/ncomms4517.

PubMed [citation]

PMID:: 24670872
PMCID:: PMC3974215

EYS is a major gene for rod-cone dystrophies in France.

Audo I, Sahel JA, Mohand-Saïd S, Lancelot ME, Antonio A, Moskova-Doumanova V, Nandrot EF, Doumanov J, Barragan I, Antinolo G, Bhattacharya SS, Zeitz C.

Hum Mutat. 2010 May;31(5):E1406-35. doi: 10.1002/humu.21249.

PubMed [citation]

PMID:: 20333770

See all PubMed Citations (6)

Details of each submission

From Ocular Genomics Institute, Massachusetts Eye and Ear, SCV001573403.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (5)

Description

The EYS c.6416G>A 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: PS1, PM2, PP1, PP3. Based on this evidence we have classified this variant as Likely 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 Revvity Omics, Revvity, SCV002024540.3

#	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

From 3billion, SCV002521640.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.014%). Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.76; 3Cnet: 0.41). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000189230). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 20237254) and to co-segregate with the disease in at least 3 similarly affected relatives/individuals in the same family or similarly affected unrelated family (PMID:20237254). A different missense change at the same codon (p.Cys2139Arg) has been reported to be associated with EYS related disorder (ClinVar ID: VCV001066550 / PMID: 25366773). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

From MGZ Medical Genetics Center, SCV002580690.1

#	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, SCV004192862.2

#	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: Nov 10, 2024

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