rs367857088

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_001142800.2(EYS):c.2813A>G(p.Lys938Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,549,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

EYS
NM_001142800.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5B:2

Conservation

PhyloP100: 1.86

Publications

2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

EYS links:

ENSG00000308351 (HGNC:):

ENSG00000308351 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 6-64902146-T-C is Benign according to our data. Variant chr6-64902146-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 194823.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.2813A>G	p.Lys938Arg	missense	Exon 18 of 43	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.2813A>G	p.Lys938Arg	missense	Exon 18 of 44	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EYS	ENST00000503581.6	TSL:5 MANE Select	c.2813A>G	p.Lys938Arg	missense	Exon 18 of 43	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7	TSL:1	c.2813A>G	p.Lys938Arg	missense	Exon 18 of 44	ENSP00000359655.3	Q5T1H1-3
ENSG00000308351	ENST00000833459.1		n.172+8852T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000428

AC:

AN:

154210

AF XY:

0.000527

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000824

Gnomad ASJ exome

AF:

0.00640

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.000460

GnomAD4 exome

AF:

0.000169

AC:

236

AN:

1397022

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

133

AN XY:

688824

show subpopulations

African (AFR)

AF:

0.0000318

AC:

AN:

31496

American (AMR)

AF:

0.000113

AC:

AN:

35384

Ashkenazi Jewish (ASJ)

AF:

0.00578

AC:

145

AN:

25104

East Asian (EAS)

AF:

0.00

AC:

AN:

35666

South Asian (SAS)

AF:

0.00

AC:

AN:

78392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49260

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.0000445

AC:

AN:

1078132

Other (OTH)

AF:

0.000639

AC:

AN:

57920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000230

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41446

American (AMR)

AF:

0.000262

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68006

Other (OTH)

AF:

0.000480

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000507

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.000643

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Retinitis pigmentosa 25 (2)

Autosomal recessive retinitis pigmentosa (1)

EYS-related disorder (1)

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.73

M_CAP

Benign

0.033

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.17

PhyloP100

1.9

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.17

REVEL

Benign

0.16

Sift

Benign

0.39

Sift4G

Benign

0.10

Polyphen

0.073

Vest4

0.12

MVP

0.33

MPC

0.016

ClinPred

0.048

GERP RS

3.3

Varity_R

0.065

gMVP

0.68

Mutation Taster

=54/46

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.49

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.49

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

Computational scores

Splicing

Publications

Other links and lift over