rs878853253

chr6-64902415-GACCATATCTTCACAGTC-G

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001142800.2(EYS):c.2710_2726del(p.Asp904GlnfsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EYS NM_001142800.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.28

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-64902415-GACCATATCTTCACAGTC-G is Pathogenic according to our data. Variant chr6-64902415-GACCATATCTTCACAGTC-G is described in ClinVar as [Pathogenic]. Clinvar id is 534.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-64902415-GACCATATCTTCACAGTC-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.2710_2726del	p.Asp904GlnfsTer17	frameshift_variant	17/43	ENST00000503581.6
EYS	NM_001292009.2	c.2710_2726del	p.Asp904GlnfsTer17	frameshift_variant	17/44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.2710_2726del	p.Asp904GlnfsTer17	frameshift_variant	17/43	5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.2710_2726del	p.Asp904GlnfsTer17	frameshift_variant	17/44	1		P2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa 25 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2008

- -

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: rs878853253; hg19: chr6-65612308;