rs778030177

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5PP5

The ENST00000342421.9(EYS):c.1765A>G(p.Arg589Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000423 in 1,606,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R589K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

EYS
ENST00000342421.9 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:4U:2

Conservation

PhyloP100: 2.65

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

EYS-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
retinitis pigmentosa 25
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

EYS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr6-65334979-C-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 639739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

PP5

Variant 6-65334981-T-C is Pathogenic according to our data. Variant chr6-65334981-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 551672.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000342421.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EYS	NM_001142800.2	MANE Select	c.1765A>G	p.Arg589Gly	missense splice_region	Exon 11 of 43	NP_001136272.1
EYS	NM_198283.2		c.1765A>G	p.Arg589Gly	missense	Exon 10 of 10	NP_938024.1
EYS	NM_001292009.2		c.1765A>G	p.Arg589Gly	missense splice_region	Exon 11 of 44	NP_001278938.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EYS	ENST00000342421.9	TSL:1	c.1765A>G	p.Arg589Gly	missense	Exon 9 of 9	ENSP00000341818.5
EYS	ENST00000503581.6	TSL:5 MANE Select	c.1765A>G	p.Arg589Gly	missense splice_region	Exon 11 of 43	ENSP00000424243.1
EYS	ENST00000370621.7	TSL:1	c.1765A>G	p.Arg589Gly	missense splice_region	Exon 11 of 44	ENSP00000359655.3

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000962

AC:

AN:

249410

AF XY:

0.000111

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.000398

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000797

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000419

AC:

AN:

1454324

Hom.:

Cov.:

AF XY:

0.0000497

AC XY:

AN XY:

723918

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33272

American (AMR)

AF:

0.000247

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.000423

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39606

South Asian (SAS)

AF:

0.00

AC:

AN:

86142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52228

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.0000289

AC:

AN:

1106702

Other (OTH)

AF:

0.0000832

AC:

AN:

60106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151772

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74116

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41388

American (AMR)

AF:

0.000132

AC:

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5132

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67830

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000552

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Retinitis pigmentosa 25 (4)

Macular dystrophy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

Eigen

Benign

0.032

Eigen_PC

Benign

0.039

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.29

PhyloP100

2.6

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.45

Sift

Benign

0.11

Sift4G

Uncertain

0.0020

Polyphen

0.96

Vest4

0.51

MVP

0.49

MPC

0.010

ClinPred

0.46

GERP RS

3.4

Varity_R

0.17

gMVP

0.85

Mutation Taster

=1/99

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.30

Position offset: -1

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over