NM_001142800.2:c.6977G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001142800.2(EYS):c.6977G>A(p.Arg2326Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,548,378 control chromosomes in the GnomAD database, including 99,961 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9478 hom., cov: 31)

Exomes 𝑓: 0.36 ( 90483 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.0350

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]

EYS links:

LOC107986608 (HGNC:):

LOC107986608 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a domain Laminin G-like 2 (size 194) in uniprot entity EYS_HUMAN there are 9 pathogenic changes around while only 3 benign (75%) in NM_001142800.2

BP4

Computational evidence support a benign effect (MetaRNN=1.9803643E-4).

BP6

Variant 6-63984461-C-T is Benign according to our data. Variant chr6-63984461-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-63984461-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.6977G>A	p.Arg2326Gln	missense_variant	Exon 35 of 43	ENST00000503581.6	NP_001136272.1	Q5T1H1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EYS	ENST00000503581.6 link	c.6977G>A	p.Arg2326Gln	missense_variant	Exon 35 of 43	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 link	c.6977G>A	p.Arg2326Gln	missense_variant	Exon 35 of 44	1		ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000398580.3 link	c.290G>A	p.Arg97Gln	missense_variant	Exon 3 of 10	5		ENSP00000381585.3	H0Y3Q4

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53322

AN:

151316

Hom.:

9479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.335

AC:

52628

AN:

156904

Hom.:

9128

AF XY:

0.344

AC XY:

28525

AN XY:

83000

show subpopulations

Gnomad AFR exome

AF:

0.378

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.364

Gnomad EAS exome

AF:

0.353

Gnomad SAS exome

AF:

0.385

Gnomad FIN exome

AF:

0.297

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.358

AC:

499678

AN:

1396944

Hom.:

90483

Cov.:

AF XY:

0.359

AC XY:

247255

AN XY:

689104

show subpopulations

Gnomad4 AFR exome

AF:

0.385

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.349

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.361

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.352

AC:

53346

AN:

151434

Hom.:

9478

Cov.:

AF XY:

0.347

AC XY:

25632

AN XY:

73952

show subpopulations

Gnomad4 AFR

AF:

0.380

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.369

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.357

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.362

Hom.:

14897

Bravo

AF:

0.353

TwinsUK

AF:

0.366

AC:

1356

ALSPAC

AF:

0.371

AC:

1431

ESP6500AA

AF:

0.384

AC:

531

ESP6500EA

AF:

0.351

AC:

1118

ExAC

AF:

0.346

AC:

8550

Asia WGS

AF:

0.342

AC:

1188

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

Jul 05, 2011

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apr 20, 2023

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 25

Benign:3

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

- -

Jul 01, 2021

Genome-Nilou Lab

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

- -

Retinitis pigmentosa

Benign:2

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. -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

0.079

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

3.5

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.00020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.090

N;N

REVEL

Benign

0.11

Sift

Benign

0.065

T;T

Sift4G

Uncertain

0.027

D;D

Polyphen

0.010

B;B

Vest4

0.098

MPC

0.015

ClinPred

0.0035

GERP RS

0.33

Varity_R

0.025

gMVP

0.75

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over