Genetic Variant EYS:c.863-22dupT (chr6-65405388-G-GA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001142800.2(EYS):c.863-22dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,478,536 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

EYS
NM_001142800.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.391

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2 link	c.863-22dupT	intron_variant	Intron 5 of 42	ENST00000503581.6	NP_001136272.1	Q5T1H1-1
EYS	NM_001292009.2 link	c.863-22dupT	intron_variant	Intron 5 of 43		NP_001278938.1	Q5T1H1-3
EYS	NM_001142801.2 link	c.863-22dupT	intron_variant	Intron 5 of 11		NP_001136273.1	Q5T1H1-4
EYS	NM_198283.2 link	c.863-22dupT	intron_variant	Intron 4 of 9		NP_938024.1	Q5T1H1-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EYS	ENST00000503581.6 link	c.863-22_863-21insT	intron_variant	Intron 5 of 42	5	NM_001142800.2	ENSP00000424243.1	Q5T1H1-1
EYS	ENST00000370621.7 link	c.863-22_863-21insT	intron_variant	Intron 5 of 43	1		ENSP00000359655.3	Q5T1H1-3
EYS	ENST00000393380.6 link	c.863-22_863-21insT	intron_variant	Intron 5 of 11	1		ENSP00000377042.2	Q5T1H1-4
EYS	ENST00000342421.9 link	c.863-22_863-21insT	intron_variant	Intron 3 of 8	1		ENSP00000341818.5	Q5T1H1-2

Frequencies

GnomAD3 genomes

AF:

0.000155

AC:

AN:

148268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000673

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00178

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000420

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000298

Gnomad OTH

AF:

0.000489

GnomAD2 exomes

AF:

0.00164

AC:

332

AN:

202572

AF XY:

0.00158

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00125

Gnomad EAS exome

AF:

0.00463

Gnomad FIN exome

AF:

0.00141

Gnomad NFE exome

AF:

0.000923

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00157

AC:

2083

AN:

1330166

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

999

AN XY:

665456

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00154

AC:

AN:

29900

American (AMR)

AF:

0.00258

AC:

AN:

37986

Ashkenazi Jewish (ASJ)

AF:

0.00121

AC:

AN:

24010

East Asian (EAS)

AF:

0.00199

AC:

AN:

37638

South Asian (SAS)

AF:

0.00293

AC:

223

AN:

76090

European-Finnish (FIN)

AF:

0.00112

AC:

AN:

51078

Middle Eastern (MID)

AF:

0.00113

AC:

AN:

5326

European-Non Finnish (NFE)

AF:

0.00146

AC:

1477

AN:

1012842

Other (OTH)

AF:

0.00130

AC:

AN:

55296

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.289

Heterozygous variant carriers

221

442

663

884

1105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.000155

AC:

AN:

148370

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

AN XY:

72240

show subpopulations

African (AFR)

AF:

0.000148

AC:

AN:

40502

American (AMR)

AF:

0.0000672

AC:

AN:

14884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00179

AC:

AN:

5040

South Asian (SAS)

AF:

0.00

AC:

AN:

4726

European-Finnish (FIN)

AF:

0.000420

AC:

AN:

9526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000299

AC:

AN:

66992

Other (OTH)

AF:

0.000485

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.00354

Hom.:

270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over