NM_001142800.2(EYS):c.8283C>G (p.Tyr2761Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 1, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001045900.7

Allele description [Variation Report for NM_001142800.2(EYS):c.8283C>G (p.Tyr2761Ter)]

NM_001142800.2(EYS):c.8283C>G (p.Tyr2761Ter)

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.8283C>G (p.Tyr2761Ter)

HGVS:

NC_000006.12:g.63721748G>C
NG_023443.2:g.1990478C>G
NM_001142800.2:c.8283C>GMANE SELECT
NM_001290259.2:c.*8040G>C
NM_001292009.2:c.8346C>G
NM_001370348.2:c.*8040G>CMANE SELECT
NM_001370349.2:c.*8040G>C
NM_001370350.2:c.*8040G>C
NM_015153.4:c.*8040G>C
NP_001136272.1:p.Tyr2761Ter
NP_001278938.1:p.Tyr2782Ter
NC_000006.11:g.64431644G>C
NM_001142800.1:c.8283C>G

Protein change:

Y2761*

Links:

dbSNP: rs1326546845

NCBI 1000 Genomes Browser:

rs1326546845

Molecular consequence:

NM_001290259.2:c.*8040G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001370348.2:c.*8040G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001370349.2:c.*8040G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001370350.2:c.*8040G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_015153.4:c.*8040G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001142800.2:c.8283C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001292009.2:c.8346C>G - 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
SCV001209775	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 1, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001209775

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 1, 2019)

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001209775.5

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the EYS protein. Another variant that disrupts this region (p.Tyr2935*) has been determined to be pathogenic (PMID:¬†22363543,¬†24652164, 28763560). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with EYS-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the EYS gene (p.Tyr2761*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 384 amino acids of the EYS protein.

#	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: Feb 28, 2024

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