rs1555454566
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Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM4PP3PP5_Very_Strong
The NM_014249.4(NR2E3):βc.194_202delβ(p.Asn65_Cys67del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000899 in 1,445,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ).
Frequency
Genomes: not found (cov: 32)
Exomes π: 0.0000090 ( 0 hom. )
Consequence
NR2E3
NM_014249.4 inframe_deletion
NM_014249.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.66
Genes affected
NR2E3 (HGNC:7974): (nuclear receptor subfamily 2 group E member 3) This protein is part of a large family of nuclear receptor transcription factors involved in signaling pathways. Nuclear receptors have been shown to regulate pathways involved in embryonic development, as well as in maintenance of proper cell function in adults. Members of this family are characterized by discrete domains that function in DNA and ligand binding. This gene encodes a retinal nuclear receptor that is a ligand-dependent transcription factor. Defects in this gene are a cause of enhanced S cone syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PM1
?
In a zinc_finger_region NR C4-type (size 20) in uniprot entity NR2E3_HUMAN there are 19 pathogenic changes around while only 0 benign (100%) in NM_014249.4
PM4
?
Nonframeshift variant in NON repetitive region in NM_014249.4.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 15-71811552-CCTGCAACGG-C is Pathogenic according to our data. Variant chr15-71811552-CCTGCAACGG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 551852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-71811552-CCTGCAACGG-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR2E3 | NM_014249.4 | c.194_202del | p.Asn65_Cys67del | inframe_deletion | 2/8 | ENST00000617575.5 | |
NR2E3 | NM_016346.4 | c.194_202del | p.Asn65_Cys67del | inframe_deletion | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR2E3 | ENST00000617575.5 | c.194_202del | p.Asn65_Cys67del | inframe_deletion | 2/8 | 1 | NM_014249.4 | P1 | |
NR2E3 | ENST00000621098.1 | c.194_202del | p.Asn65_Cys67del | inframe_deletion | 2/7 | 1 | |||
NR2E3 | ENST00000621736.4 | c.-71_-63del | 5_prime_UTR_variant | 4/10 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.0000135 AC: 3AN: 222772Hom.: 0 AF XY: 0.00000830 AC XY: 1AN XY: 120544
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GnomAD4 exome AF: 0.00000899 AC: 13AN: 1445784Hom.: 0 AF XY: 0.00000976 AC XY: 7AN XY: 717570
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Enhanced S-cone syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 20, 2024 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 17, 2020 | - - |
Enhanced S-cone syndrome;C1970163:Retinitis pigmentosa 37 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 09, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 21, 2021 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 29, 2023 | For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 551852). This variant has been observed in individual(s) with autosomal recessive enhanced S-cone syndrome/Goldmann-Favre syndrome (PMID: 12963616, 19273793, 19898638, 21364904, 28541266). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.008%). This variant, c.194_202del, results in the deletion of 3 amino acid(s) of the NR2E3 protein (p.Asn65_Cys67del), but otherwise preserves the integrity of the reading frame. - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Aug 13, 2019 | - - |
Retinitis pigmentosa Pathogenic:1
Pathogenic, no assertion criteria provided | research | Sharon lab, Hadassah-Hebrew University Medical Center | Jun 23, 2019 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at