6-64307084-TGAGAGAGAGAGA-TGAGAGAGAGAGAGAGA

Variant names:

• chr6-64307084-T-TGAGA
• rs35395170
• NM_001142800.2:c.6079-6_6079-3dupTCTC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001142800.2(EYS):​c.6079-6_6079-3dupTCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: EYS NM_001142800.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0860
• Publications: 8 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 6-64307084-T-TGAGA is Benign according to our data. Variant chr6-64307084-T-TGAGA is described in ClinVar as Likely_benign. ClinVar VariationId is 1086951.Status of the report is criteria_provided_single_submitter, 1 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	NM_001142800.2	MANE Select	c.6079-6_6079-3dupTCTC		splice_region intron	N/A	NP_001136272.1
	EYS	NM_001292009.2		c.6079-6_6079-3dupTCTC		splice_region intron	N/A	NP_001278938.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.6079-3_6079-2insTCTC		splice_region intron	N/A	ENSP00000424243.1
	EYS	ENST00000370621.7	TSL:1	c.6079-3_6079-2insTCTC		splice_region intron	N/A	ENSP00000359655.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000107 AC: 1 AN: 93566 AF XY: 0.0000202

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000270

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 6 AN: 731202 Hom.: 0 Cov.: 0 AF XY: 0.0000105 AC XY: 4 AN XY: 381320

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

African (AFR) AF: 0.00 AC: 0 AN: 17816

American (AMR) AF: 0.00 AC: 0 AN: 27610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19614

East Asian (EAS) AF: 0.00 AC: 0 AN: 31412

South Asian (SAS) AF: 0.00 AC: 0 AN: 59514

European-Finnish (FIN) AF: 0.0000225 AC: 1 AN: 44540

Middle Eastern (MID) AF: 0.000240 AC: 1 AN: 4170

European-Non Finnish (NFE) AF: 0.00000815 AC: 4 AN: 491076

Other (OTH) AF: 0.00 AC: 0 AN: 35450

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000691896), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 2265

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 18, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.086

Splicing

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

Other links and lift over

dbSNP: rs35395170; hg19: chr6-65016977;