chr12-88111320-A-C
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_025114.4(CEP290):āc.2249T>Gā(p.Leu750Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000447 in 1,564,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (ā ā ). Synonymous variant affecting the same amino acid position (i.e. L750L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_025114.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CEP290 | NM_025114.4 | c.2249T>G | p.Leu750Ter | stop_gained | 22/54 | ENST00000552810.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CEP290 | ENST00000552810.6 | c.2249T>G | p.Leu750Ter | stop_gained | 22/54 | 1 | NM_025114.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152086Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000532 AC: 1AN: 187888Hom.: 0 AF XY: 0.00000987 AC XY: 1AN XY: 101276
GnomAD4 exome AF: 0.00000354 AC: 5AN: 1412640Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 2AN XY: 699360
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74278
ClinVar
Submissions by phenotype
Leber congenital amaurosis 10 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2006 | - - |
Bardet-Biedl syndrome 14 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 14, 2023 | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 02, 2023 | This sequence change creates a premature translational stop signal (p.Leu750*) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). This variant is present in population databases (rs137852833, gnomAD 0.001%). This premature translational stop signal has been observed in individual(s) with leber congenital amaurosis (PMID: 16909394, 28559085). ClinVar contains an entry for this variant (Variation ID: 1338). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at