6-64307084-TGAGAGAGAGAGA-TGAGAGA

Position:

• chr6-64307084-TGAGAGAGAGAGA-TGAGAGA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP6_Very_Strong

The NM_001142800.2(EYS):​c.6079-8_6079-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000901 in 872,158 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: EYS NM_001142800.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: 0.762

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-64307084-TGAGAGA-T is Benign according to our data. Variant chr6-64307084-TGAGAGA-T is described in ClinVar as [Benign]. Clinvar id is 726159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6079-8_6079-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.6079-8_6079-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6079-8_6079-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001142800.2	ENSP00000424243	A2
EYS	ENST00000370621.7	c.6079-8_6079-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000359655	P2

Frequencies

GnomAD3 genomes AF: 0.000127 AC: 19 AN: 149932 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000734

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000238

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00106 AC: 767 AN: 722226 Hom.: 0 AF XY: 0.00109 AC XY: 410 AN XY: 376678

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.000622

Gnomad4 EAS exome AF: 0.000513

Gnomad4 SAS exome AF: 0.00113

Gnomad4 FIN exome AF: 0.000318

Gnomad4 NFE exome AF: 0.00117

Gnomad4 OTH exome AF: 0.000800

GnomAD4 genome AF: 0.000127 AC: 19 AN: 149932 Hom.: 0 Cov.: 0 AF XY: 0.0000959 AC XY: 7 AN XY: 73014

Gnomad4 AFR AF: 0.0000734

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000238

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Retinitis pigmentosa 25 Uncertain:1 Benign:1

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 02, 2023	- -
Uncertain significance, no assertion criteria provided	clinical testing	Natera, Inc.	Jan 24, 2020	- -

EYS-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 06, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35395170; hg19: chr6-65016977;