NM_001142800.2:c.6079-14_6079-3delTCTCTCTCTCTC

Variant names:

• chr6-64307084-TGAGAGAGAGAGA-T
• rs35395170
• NM_001142800.2:c.6079-14_6079-3delTCTCTCTCTCTC

Variant summary

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

The NM_001142800.2(EYS):​c.6079-14_6079-3delTCTCTCTCTCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 731,206 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: EYS NM_001142800.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.937
• Publications: 0 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-TGAGAGAGAGAGA-T is Benign according to our data. Variant chr6-64307084-TGAGAGAGAGAGA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1566215.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6079-14_6079-3delTCTCTCTCTCTC		splice_region_variant, intron_variant	Intron 29 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.6079-14_6079-3delTCTCTCTCTCTC		splice_region_variant, intron_variant	Intron 29 of 43		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6079-14_6079-3delTCTCTCTCTCTC		splice_region_variant, intron_variant	Intron 29 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.6079-14_6079-3delTCTCTCTCTCTC		splice_region_variant, intron_variant	Intron 29 of 43	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000274 AC: 2 AN: 731206 Hom.: 0 AF XY: 0.00 AC XY: 0 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: 31414

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4170

European-Non Finnish (NFE) AF: 0.00000407 AC: 2 AN: 491078

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

⚠️ 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 Cov.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 20, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.94

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;