NM_001142800.2(EYS):c.8545C>T (p.Arg2849Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 17, 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:: RCV000597091.8

Allele description [Variation Report for NM_001142800.2(EYS):c.8545C>T (p.Arg2849Ter)]

NM_001142800.2(EYS):c.8545C>T (p.Arg2849Ter)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

6q12

Genomic location:

Preferred name:

NM_001142800.2(EYS):c.8545C>T (p.Arg2849Ter)

HGVS:

NC_000006.12:g.63721486G>A
NG_023443.2:g.1990740C>T
NG_034034.2:g.90686G>A
NM_001142800.2:c.8545C>TMANE SELECT
NM_001290259.2:c.*7778G>A
NM_001292009.2:c.8608C>T
NM_001370348.2:c.*7778G>AMANE SELECT
NM_001370349.2:c.*7778G>A
NM_001370350.2:c.*7778G>A
NM_015153.4:c.*7778G>A
NP_001136272.1:p.Arg2849Ter
NP_001278938.1:p.Arg2870Ter
NC_000006.11:g.64431382G>A
NM_001142800.1:c.8545C>T

Protein change:

R2849*

Links:

dbSNP: rs1326635278

NCBI 1000 Genomes Browser:

rs1326635278

Molecular consequence:

NM_001290259.2:c.*7778G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001370348.2:c.*7778G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001370349.2:c.*7778G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001370350.2:c.*7778G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_015153.4:c.*7778G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001142800.2:c.8545C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001292009.2:c.8608C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000709699	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Sep 7, 2017)	germline	clinical testing	Citation Link,
SCV000959359	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22363543, 24652164, 28763560, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000709699

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Sep 7, 2017)

germline

clinical testing

Citation Link,

SCV000959359

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 17, 2023)

germline

clinical testing

PubMed (4)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Autosomal recessive cone-rod dystrophy associated with compound heterozygous mutations in the EYS gene.

Katagiri S, Akahori M, Hayashi T, Yoshitake K, Gekka T, Ikeo K, Tsuneoka H, Iwata T.

Doc Ophthalmol. 2014 Jun;128(3):211-7. doi: 10.1007/s10633-014-9435-0. Epub 2014 Mar 21.

PubMed [citation]

PMID:: 24652164

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000709699.1

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

Description

The R2870X nonsense variant in the EYS gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It is predicted to cause loss of normal protein function through protein truncation. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In summary, we consider this variant to be 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000959359.4

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

Description

This sequence change creates a premature translational stop signal (p.Arg2849*) in the EYS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 296 amino acid(s) of the EYS protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EYS-related conditions. ClinVar contains an entry for this variant (Variation ID: 503517). This variant disrupts a region of the EYS protein in which other variant(s) (p.Tyr2935*) have been determined to be pathogenic (PMID: 22363543, 24652164, 28763560). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been 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: Sep 29, 2024

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