12-88049237-AAGC-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_025114.4(CEP290):βc.7384_7386delβ(p.Ala2462del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,608,648 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ). Synonymous variant affecting the same amino acid position (i.e. A2462A) has been classified as Likely benign.
Frequency
Consequence
NM_025114.4 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP290 | NM_025114.4 | c.7384_7386del | p.Ala2462del | inframe_deletion | 54/54 | ENST00000552810.6 | |
RLIG1 | NM_001009894.3 | c.*820_*822del | 3_prime_UTR_variant | 7/7 | ENST00000356891.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP290 | ENST00000552810.6 | c.7384_7386del | p.Ala2462del | inframe_deletion | 54/54 | 1 | NM_025114.4 | P4 | |
RLIG1 | ENST00000356891.4 | c.*820_*822del | 3_prime_UTR_variant | 7/7 | 1 | NM_001009894.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152018Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1456630Hom.: 0 AF XY: 0.00000276 AC XY: 2AN XY: 724254
GnomAD4 genome AF: 0.000138 AC: 21AN: 152018Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74242
ClinVar
Submissions by phenotype
Leber congenital amaurosis Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This variant, c.7384_7386del, results in the deletion of 1 amino acid(s) of the CEP290 protein (p.Ala2462del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CEP290-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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