6-65405388-GA-GAAA

Variant names:

• chr6-65405388-G-GAA
• rs34154043
• NM_001142800.2:c.863-23_863-22dupTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001142800.2(EYS):​c.863-23_863-22dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,469,002 control chromosomes in the GnomAD database, including 20,765 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4035 hom., cov: 0)
  • Exomes 𝑓: 0.21 (16730 hom.)
• Consequence: EYS NM_001142800.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.391
• Publications: 4 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-65405388-G-GAA is Benign according to our data. Variant chr6-65405388-G-GAA is described in CliVar as Benign. Clinvar id is 1225094.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAA is described in CliVar as Benign. Clinvar id is 1225094.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAA is described in CliVar as Benign. Clinvar id is 1225094.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAA is described in CliVar as Benign. Clinvar id is 1225094.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAA is described in CliVar as Benign. Clinvar id is 1225094.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAA is described in CliVar as Benign. Clinvar id is 1225094.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAA is described in CliVar as Benign. Clinvar id is 1225094.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-65405388-G-GAA is described in CliVar as Benign. Clinvar id is 1225094.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.863-23_863-22dupTT		intron_variant	Intron 5 of 42	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.863-23_863-22dupTT		intron_variant	Intron 5 of 43		NP_001278938.1
EYS	NM_001142801.2	c.863-23_863-22dupTT		intron_variant	Intron 5 of 11		NP_001136273.1
EYS	NM_198283.2	c.863-23_863-22dupTT		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_863-21insTT		intron_variant	Intron 5 of 42	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.863-22_863-21insTT		intron_variant	Intron 5 of 43	1		ENSP00000359655.3
EYS	ENST00000393380.6	c.863-22_863-21insTT		intron_variant	Intron 5 of 11	1		ENSP00000377042.2
EYS	ENST00000342421.9	c.863-22_863-21insTT		intron_variant	Intron 3 of 8	1		ENSP00000341818.5

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34198 AN: 148036 Hom.: 4024 Cov.: 0

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.220

GnomAD2 exomes AF: 0.234 AC: 47327 AN: 202572 AF XY: 0.234

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.209

Gnomad EAS exome AF: 0.260

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.207 AC: 273176 AN: 1320876 Hom.: 16730 Cov.: 25 AF XY: 0.209 AC XY: 138299 AN XY: 660614

African (AFR) AF: 0.229 AC: 6828 AN: 29876

American (AMR) AF: 0.260 AC: 9783 AN: 37656

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 4846 AN: 23856

East Asian (EAS) AF: 0.246 AC: 9247 AN: 37542

South Asian (SAS) AF: 0.298 AC: 22626 AN: 75966

European-Finnish (FIN) AF: 0.229 AC: 11560 AN: 50470

Middle Eastern (MID) AF: 0.182 AC: 967 AN: 5302

European-Non Finnish (NFE) AF: 0.195 AC: 195969 AN: 1005262

Other (OTH) AF: 0.207 AC: 11350 AN: 54946

GnomAD4 genome AF: 0.231 AC: 34244 AN: 148126 Hom.: 4035 Cov.: 0 AF XY: 0.237 AC XY: 17066 AN XY: 72104

African (AFR) AF: 0.257 AC: 10386 AN: 40432

American (AMR) AF: 0.213 AC: 3161 AN: 14850

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 801 AN: 3446

East Asian (EAS) AF: 0.277 AC: 1396 AN: 5032

South Asian (SAS) AF: 0.351 AC: 1656 AN: 4714

European-Finnish (FIN) AF: 0.249 AC: 2356 AN: 9478

Middle Eastern (MID) AF: 0.162 AC: 47 AN: 290

European-Non Finnish (NFE) AF: 0.208 AC: 13894 AN: 66924

Other (OTH) AF: 0.220 AC: 454 AN: 2060

Alfa AF: 0.160 Hom.: 270

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 25 Benign:1

Sep 27, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs34154043; hg19: chr6-66115281;