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

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 31, 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:: RCV001723741.5

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]

Condition(s)

Name:: Retinitis pigmentosa (RP)
Synonyms:: Tapetoretinal degeneration
Identifiers:: MONDO: MONDO:0019200; MeSH: D012174; MedGen: C0035334; Orphanet: 791; OMIM: 268000; OMIM: PS268000

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001950257	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 1, 2021)	germline	curation	PubMed (6) [See all records that cite these PMIDs] 24670872, 20333770, 20237254, 27375351, 25741868, 34906470
SCV005202439	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jul 31, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27375351, 20333770, 25753737 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001950257

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 1, 2021)

germline

curation

PubMed (6)
[See all records that cite these PMIDs]

SCV005202439

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jul 31, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	curation
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

Identification of novel mutations in the ortholog of Drosophila eyes shut gene (EYS) causing autosomal recessive retinitis pigmentosa.

Abd El-Aziz MM, O'Driscoll CA, Kaye RS, Barragan I, El-Ashry MF, Borrego S, Antiñolo G, Pang CP, Webster AR, Bhattacharya SS.

Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4266-72. doi: 10.1167/iovs.09-5109. Epub 2010 Mar 17. Erratum in: Invest Ophthalmol Vis Sci. 2014 Dec;55(12):8055.

PubMed [citation]

PMID:: 20237254

See all PubMed Citations (7)

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001950257.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (6)

Description

The p.Cys2139Tyr variant in EYS was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). 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. If you have any questions about the classification please reach out to the Pierce Lab.

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005202439.1

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

Description

Variant summary: EYS c.6416G>A (p.Cys2139Tyr) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 152386 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in EYS causing Retinitis Pigmentosa (0.00014 vs 0.0034), allowing no conclusion about variant significance. c.6416G>A has been reported in the literature as compound heterozygous or homozygous genotype in multiple individuals affected with autosomal ecessive Retinitis Pigmentosa (Rudo_2010, Chen_2015, Gu_2016). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 20333770, 25753737, 27375351). ClinVar contains an entry for this variant (Variation ID: 189230). Based on the evidence outlined above, the variant was classified as pathogenic.

#	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: Oct 8, 2024

ClinVar

Relating variation to medicine