6-64912570-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142800.2(EYS):​c.2555T>C​(p.Leu852Pro) variant causes a missense change. The variant allele was found at a frequency of 0.593 in 1,550,694 control chromosomes in the GnomAD database, including 276,892 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 34884 hom., cov: 32)
Exomes 𝑓: 0.59 ( 242008 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 4.23
Variant links:
Genes affected
EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=3.853312E-6).
BP6
Variant 6-64912570-A-G is Benign according to our data. Variant chr6-64912570-A-G is described in ClinVar as [Benign]. Clinvar id is 93605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-64912570-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EYSNM_001142800.2 linkc.2555T>C p.Leu852Pro missense_variant Exon 16 of 43 ENST00000503581.6 NP_001136272.1 Q5T1H1-1
EYSNM_001292009.2 linkc.2555T>C p.Leu852Pro missense_variant Exon 16 of 44 NP_001278938.1 Q5T1H1-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EYSENST00000503581.6 linkc.2555T>C p.Leu852Pro missense_variant Exon 16 of 43 5 NM_001142800.2 ENSP00000424243.1 Q5T1H1-1
EYSENST00000370621.7 linkc.2555T>C p.Leu852Pro missense_variant Exon 16 of 44 1 ENSP00000359655.3 Q5T1H1-3

Frequencies

GnomAD3 genomes
AF:
0.664
AC:
100789
AN:
151842
Hom.:
34846
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.871
Gnomad AMI
AF:
0.557
Gnomad AMR
AF:
0.641
Gnomad ASJ
AF:
0.699
Gnomad EAS
AF:
0.408
Gnomad SAS
AF:
0.555
Gnomad FIN
AF:
0.577
Gnomad MID
AF:
0.630
Gnomad NFE
AF:
0.583
Gnomad OTH
AF:
0.654
GnomAD3 exomes
AF:
0.593
AC:
92797
AN:
156496
Hom.:
28224
AF XY:
0.586
AC XY:
48635
AN XY:
82932
show subpopulations
Gnomad AFR exome
AF:
0.882
Gnomad AMR exome
AF:
0.619
Gnomad ASJ exome
AF:
0.695
Gnomad EAS exome
AF:
0.402
Gnomad SAS exome
AF:
0.559
Gnomad FIN exome
AF:
0.580
Gnomad NFE exome
AF:
0.580
Gnomad OTH exome
AF:
0.612
GnomAD4 exome
AF:
0.585
AC:
818369
AN:
1398734
Hom.:
242008
Cov.:
42
AF XY:
0.583
AC XY:
402451
AN XY:
689884
show subpopulations
Gnomad4 AFR exome
AF:
0.887
Gnomad4 AMR exome
AF:
0.626
Gnomad4 ASJ exome
AF:
0.693
Gnomad4 EAS exome
AF:
0.437
Gnomad4 SAS exome
AF:
0.562
Gnomad4 FIN exome
AF:
0.579
Gnomad4 NFE exome
AF:
0.578
Gnomad4 OTH exome
AF:
0.605
GnomAD4 genome
AF:
0.664
AC:
100881
AN:
151960
Hom.:
34884
Cov.:
32
AF XY:
0.660
AC XY:
49037
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.871
Gnomad4 AMR
AF:
0.641
Gnomad4 ASJ
AF:
0.699
Gnomad4 EAS
AF:
0.408
Gnomad4 SAS
AF:
0.554
Gnomad4 FIN
AF:
0.577
Gnomad4 NFE
AF:
0.583
Gnomad4 OTH
AF:
0.655
Alfa
AF:
0.600
Hom.:
55242
Bravo
AF:
0.675
TwinsUK
AF:
0.586
AC:
2172
ALSPAC
AF:
0.568
AC:
2189
ESP6500AA
AF:
0.878
AC:
1215
ESP6500EA
AF:
0.575
AC:
1831
ExAC
AF:
0.595
AC:
14197
Asia WGS
AF:
0.556
AC:
1934
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:13
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Retinitis pigmentosa 25 Benign:5
Mar 04, 2015
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Nov 29, 2023
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

May 28, 2019
Mendelics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jul 01, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:3
Apr 17, 2023
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Sep 19, 2013
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:2
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jul 05, 2011
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The variant is found in ARRP panel(s). -

Retinitis pigmentosa Benign:2
Sep 16, 2020
Natera, Inc.
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Retinal dystrophy Benign:1
Oct 01, 2023
Dept Of Ophthalmology, Nagoya University
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.042
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
12
DANN
Benign
0.080
DEOGEN2
Benign
0.029
.;T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.14
T;T
MetaRNN
Benign
0.0000039
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.56
N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
4.3
N;N
REVEL
Benign
0.13
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;.
Vest4
0.059
MPC
0.0093
ClinPred
0.0061
T
GERP RS
3.1
Varity_R
0.047
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9294631; hg19: chr6-65622463; COSMIC: COSV65505165; API