rs9294631

Variant names:

• chr6-64912570-A-C
• rs9294631
• NM_001142800.2:c.2555T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-64912570-A-C
• chr6-64912570-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142800.2(EYS):​c.2555T>G​(p.Leu852Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L852P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EYS NM_001142800.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• Publications: 39 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

ENSG00000308351 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22468895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.2555T>G	p.Leu852Arg	missense_variant	Exon 16 of 43	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.2555T>G	p.Leu852Arg	missense_variant	Exon 16 of 44		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.2555T>G	p.Leu852Arg	missense_variant	Exon 16 of 43	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.2555T>G	p.Leu852Arg	missense_variant	Exon 16 of 44	1		ENSP00000359655.3
ENSG00000308351	ENST00000833459.1	n.173-3753A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.040	.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.64	N;N
PhyloP100		4.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.8	N;N
REVEL	Benign	0.20
Sift	Benign	0.081	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0010	B;.
Vest4		0.20
MutPred		0.55		Loss of stability (P = 0.0358);Loss of stability (P = 0.0358);
MVP		0.51
MPC		0.010
ClinPred		0.31	T
GERP RS		3.1
Varity_R		0.052
gMVP		0.88
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs9294631; hg19: chr6-65622463;