6-64307084-TGAGAGAGAGAGA-TGAGA

Position:

• chr6-64307084-TGAGAGAGAGAGA-TGAGA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001142800.2(EYS):​c.6079-10_6079-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000386 in 881,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: EYS NM_001142800.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.762

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-64307084-TGAGAGAGA-T is Benign according to our data. Variant chr6-64307084-TGAGAGAGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1530693.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYS	NM_001142800.2	c.6079-10_6079-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.6079-10_6079-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.6079-10_6079-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001142800.2	ENSP00000424243	A2
EYS	ENST00000370621.7	c.6079-10_6079-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000359655	P2

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 4 AN: 149972 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000489

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000410 AC: 30 AN: 731046 Hom.: 0 AF XY: 0.0000393 AC XY: 15 AN XY: 381244

Gnomad4 AFR exome AF: 0.0000561

Gnomad4 AMR exome AF: 0.0000362

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000168

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000530

Gnomad4 OTH exome AF: 0.0000282

GnomAD4 genome AF: 0.0000267 AC: 4 AN: 150076 Hom.: 0 Cov.: 0 AF XY: 0.0000273 AC XY: 2 AN XY: 73152

Gnomad4 AFR AF: 0.0000488

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000297

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 28, 2022

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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: rs35395170; hg19: chr6-65016977;