chr12-88049208-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_025114.4(CEP290):c.7416T>A(p.Ser2472Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S2472S) has been classified as Likely benign.
Frequency
Consequence
NM_025114.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP290 | NM_025114.4 | c.7416T>A | p.Ser2472Arg | missense_variant | 54/54 | ENST00000552810.6 | |
RLIG1 | NM_001009894.3 | c.*786A>T | 3_prime_UTR_variant | 7/7 | ENST00000356891.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP290 | ENST00000552810.6 | c.7416T>A | p.Ser2472Arg | missense_variant | 54/54 | 1 | NM_025114.4 | P4 | |
RLIG1 | ENST00000356891.4 | c.*786A>T | 3_prime_UTR_variant | 7/7 | 1 | NM_001009894.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151948Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000138 AC: 2AN: 1446236Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 718578
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151948Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74220
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 22, 2015 | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 2472 of the CEP290 protein (p.Ser2472Arg). This variant is present in population databases (rs794727762, gnomAD 0.01%). 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: 197973). 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: "Possibly 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at