6-65405388-GA-GAA

Variant names:

• chr6-65405388-G-GA
• rs34154043
• NM_001142800.2:c.863-22dupT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142800.2(EYS):​c.863-22dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,478,536 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0016 (1 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.863-22dupT		intron_variant	Intron 5 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.863-22dupT		intron_variant	Intron 5 of 43		NP_001278938.1
EYS	NM_001142801.2	c.863-22dupT		intron_variant	Intron 5 of 11		NP_001136273.1
EYS	NM_198283.2	c.863-22dupT		intron_variant	Intron 4 of 9		NP_938024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.863-22_863-21insT		intron_variant	Intron 5 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.863-22_863-21insT		intron_variant	Intron 5 of 43	1		ENSP00000359655.3
EYS	ENST00000393380.6	c.863-22_863-21insT		intron_variant	Intron 5 of 11	1		ENSP00000377042.2
EYS	ENST00000342421.9	c.863-22_863-21insT		intron_variant	Intron 3 of 8	1		ENSP00000341818.5

Frequencies

GnomAD3 genomes AF: 0.000155 AC: 23 AN: 148268 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000673

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00178

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000420

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000298

Gnomad OTH AF: 0.000489

GnomAD3 exomes AF: 0.00164 AC: 332 AN: 202572 Hom.: 0 AF XY: 0.00158 AC XY: 175 AN XY: 110630

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.00125

Gnomad EAS exome AF: 0.00463

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.00141

Gnomad NFE exome AF: 0.000923

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00157 AC: 2083 AN: 1330166 Hom.: 1 Cov.: 25 AF XY: 0.00150 AC XY: 999 AN XY: 665456

Gnomad4 AFR exome AF: 0.00154

Gnomad4 AMR exome AF: 0.00258

Gnomad4 ASJ exome AF: 0.00121

Gnomad4 EAS exome AF: 0.00199

Gnomad4 SAS exome AF: 0.00293

Gnomad4 FIN exome AF: 0.00112

Gnomad4 NFE exome AF: 0.00146

Gnomad4 OTH exome AF: 0.00130

GnomAD4 genome AF: 0.000155 AC: 23 AN: 148370 Hom.: 0 Cov.: 0 AF XY: 0.000152 AC XY: 11 AN XY: 72240

Gnomad4 AFR AF: 0.000148

Gnomad4 AMR AF: 0.0000672

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00179

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000420

Gnomad4 NFE AF: 0.0000299

Gnomad4 OTH AF: 0.000485

ClinVar

Not reported in ClinVar

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: rs34154043; hg19: chr6-66115281;