Genetic Variant EYS:c.2023+15dupT (chr6-65295847-G-GA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001142800.2(EYS):c.2023+15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 22197 hom., cov: 0)

Exomes 𝑓: 0.49 ( 87833 hom. )

Failed GnomAD Quality Control

Consequence

EYS
NM_001142800.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.679

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

EYS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 6-65295847-G-GA is Benign according to our data. Variant chr6-65295847-G-GA is described in ClinVar as Benign. ClinVar VariationId is 357735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

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.2023+15dupT		intron	N/A	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.2023+15dupT		intron	N/A	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EYS	ENST00000503581.6	TSL:5 MANE Select	c.2023+15dupT	intron	N/A	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7	TSL:1	c.2023+15dupT	intron	N/A	ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000370615.3	TSL:3	n.476dupT	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

77750

AN:

149522

Hom.:

22191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.735

Gnomad AMR

AF:

0.665

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.898

Gnomad SAS

AF:

0.677

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.579

GnomAD2 exomes

AF:

0.491

AC:

44607

AN:

90928

AF XY:

0.486

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.567

Gnomad ASJ exome

AF:

0.435

Gnomad EAS exome

AF:

0.655

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.478

Gnomad OTH exome

AF:

0.482

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.491

AC:

600699

AN:

1223206

Hom.:

87833

Cov.:

AF XY:

0.492

AC XY:

296491

AN XY:

603158

show subpopulations

African (AFR)

AF:

0.277

AC:

7077

AN:

25504

American (AMR)

AF:

0.543

AC:

12596

AN:

23206

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

9669

AN:

21956

East Asian (EAS)

AF:

0.643

AC:

19430

AN:

30226

South Asian (SAS)

AF:

0.515

AC:

32594

AN:

63342

European-Finnish (FIN)

AF:

0.482

AC:

21135

AN:

43804

Middle Eastern (MID)

AF:

0.474

AC:

2453

AN:

5174

European-Non Finnish (NFE)

AF:

0.491

AC:

470965

AN:

959186

Other (OTH)

AF:

0.488

AC:

24780

AN:

50808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

14807

29614

44420

59227

74034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15814

31628

47442

63256

79070

<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:

0.520

AC:

77766

AN:

149608

Hom.:

22197

Cov.:

AF XY:

0.527

AC XY:

38434

AN XY:

72962

show subpopulations

African (AFR)

AF:

0.277

AC:

11247

AN:

40650

American (AMR)

AF:

0.665

AC:

9981

AN:

15002

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

1771

AN:

3450

East Asian (EAS)

AF:

0.897

AC:

4612

AN:

5140

South Asian (SAS)

AF:

0.677

AC:

3228

AN:

4766

European-Finnish (FIN)

AF:

0.568

AC:

5686

AN:

10012

Middle Eastern (MID)

AF:

0.521

AC:

151

AN:

290

European-Non Finnish (NFE)

AF:

0.583

AC:

39209

AN:

67310

Other (OTH)

AF:

0.583

AC:

1212

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1669

3339

5008

6678

8347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

686

1372

2058

2744

3430

<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:

0.414

Hom.:

1193

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Retinitis Pigmentosa, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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6-65295847-GAA-GAAA

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