rs369104382
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_025114.4(CEP290):c.2098C>T(p.His700Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000998 in 1,603,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H700R) has been classified as Uncertain significance.
Frequency
Consequence
NM_025114.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP290 | NM_025114.4 | c.2098C>T | p.His700Tyr | missense_variant | 21/54 | ENST00000552810.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP290 | ENST00000552810.6 | c.2098C>T | p.His700Tyr | missense_variant | 21/54 | 1 | NM_025114.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000724 AC: 11AN: 151934Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 240948Hom.: 0 AF XY: 0.00000763 AC XY: 1AN XY: 131146
GnomAD4 exome AF: 0.00000344 AC: 5AN: 1451744Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2AN XY: 721886
GnomAD4 genome AF: 0.0000724 AC: 11AN: 151934Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 5AN XY: 74204
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 14, 2021 | The c.2098C>T (p.H700Y) alteration is located in exon 21 (coding exon 20) of the CEP290 gene. This alteration results from a C to T substitution at nucleotide position 2098, causing the histidine (H) at amino acid position 700 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Leber congenital amaurosis Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 07, 2022 | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 700 of the CEP290 protein (p.His700Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 461778). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Senior-Loken syndrome 6;C1857780:Joubert syndrome 5;C1857821:Leber congenital amaurosis 10;C1970161:Meckel syndrome, type 4;C2673874:Bardet-Biedl syndrome 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 18, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at