6-65295847-GAA-GAAAA

Variant names:

• chr6-65295847-G-GAA
• rs35045551
• NM_001142800.2:c.2023+14_2023+15dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_001142800.2(EYS):​c.2023+14_2023+15dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,272,354 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 0)
  • Exomes 𝑓: 0.030 (0 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.679
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP6: Variant 6-65295847-G-GAA is Benign according to our data. Variant chr6-65295847-G-GAA is described in ClinVar as Benign. ClinVar VariationId is 811241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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+14_2023+15dupTT		intron	N/A	NP_001136272.1	Q5T1H1-1
	EYS	NM_001292009.2		c.2023+14_2023+15dupTT		intron	N/A	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.2023+14_2023+15dupTT		intron	N/A	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.2023+14_2023+15dupTT		intron	N/A	ENSP00000359655.3	Q5T1H1-3
	EYS	ENST00000370615.3	TSL:3	n.475_476dupTT		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.000314 AC: 47 AN: 149544 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000739

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00140

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000297

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0456 AC: 4145 AN: 90928 AF XY: 0.0443

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.0899

Gnomad ASJ exome AF: 0.0226

Gnomad EAS exome AF: 0.159

Gnomad FIN exome AF: 0.0187

Gnomad NFE exome AF: 0.0337

Gnomad OTH exome AF: 0.0467

GnomAD4 exome AF: 0.0299 AC: 33615 AN: 1122724 Hom.: 0 Cov.: 35 AF XY: 0.0301 AC XY: 16584 AN XY: 550368

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

African (AFR) AF: 0.00625 AC: 168 AN: 26882

American (AMR) AF: 0.0694 AC: 1398 AN: 20134

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 440 AN: 20598

East Asian (EAS) AF: 0.0967 AC: 1968 AN: 20356

South Asian (SAS) AF: 0.0423 AC: 2301 AN: 54448

European-Finnish (FIN) AF: 0.0203 AC: 815 AN: 40172

Middle Eastern (MID) AF: 0.0170 AC: 84 AN: 4932

European-Non Finnish (NFE) AF: 0.0282 AC: 25041 AN: 888886

Other (OTH) AF: 0.0302 AC: 1400 AN: 46316

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000314 AC: 47 AN: 149630 Hom.: 0 Cov.: 0 AF XY: 0.000370 AC XY: 27 AN XY: 72974

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

African (AFR) AF: 0.0000737 AC: 3 AN: 40688

American (AMR) AF: 0.000133 AC: 2 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5136

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4770

European-Finnish (FIN) AF: 0.00140 AC: 14 AN: 10004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000297 AC: 20 AN: 67312

Other (OTH) AF: 0.00 AC: 0 AN: 2084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000276948), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0416 Hom.: 1193

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa 25 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs35045551; hg19: chr6-66005740;