rs1346842287

chr6-64081881-GT-G

Variant summary

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

The NM_001142800.2(EYS):c.6545del(p.Asn2182ThrfsTer3) 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 Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. N2182N) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EYS NM_001142800.2 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: -0.0190

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 6-64081881-GT-G is Pathogenic according to our data. Variant chr6-64081881-GT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438206.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-64081881-GT-G is described in Lovd as [Pathogenic]. Variant chr6-64081881-GT-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYS	NM_001142800.2	c.6545del	p.Asn2182ThrfsTer3	frameshift_variant	32/43	ENST00000503581.6
EYS	NM_001292009.2	c.6545del	p.Asn2182ThrfsTer3	frameshift_variant	32/44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYS	ENST00000503581.6	c.6545del	p.Asn2182ThrfsTer3	frameshift_variant	32/43	5	NM_001142800.2	A2
EYS	ENST00000370621.7	c.6545del	p.Asn2182ThrfsTer3	frameshift_variant	32/44	1		P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa 25 Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Genomics England Pilot Project, Genomics England

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- -

Retinitis pigmentosa Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

NIHR Bioresource Rare Diseases, University of Cambridge

Jan 01, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1346842287; hg19: chr6-64791774;