rs869320726
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_006269.2(RP1):c.2285_2289delTAAAT(p.Leu762TyrfsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_006269.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RP1 | ENST00000220676.2 | c.2285_2289delTAAAT | p.Leu762TyrfsTer17 | frameshift_variant | Exon 4 of 4 | 1 | NM_006269.2 | ENSP00000220676.1 | ||
RP1 | ENST00000637698.1 | c.787+3879_787+3883delTAAAT | intron_variant | Intron 3 of 28 | 5 | ENSP00000490104.1 | ||||
RP1 | ENST00000636932.1 | c.787+3879_787+3883delTAAAT | intron_variant | Intron 3 of 22 | 5 | ENSP00000489857.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460156Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726362
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:3
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This sequence change creates a premature translational stop signal (p.Leu762Tyrfs*17) in the RP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1395 amino acid(s) of the RP1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 10391211, 29843741). It has also been observed to segregate with disease in related individuals. This variant is also known as Leu762(5-bp del). ClinVar contains an entry for this variant (Variation ID: 5966). This variant disrupts the C-terminus of the RP1 protein. Many variants that disrupt this region have been reported in individuals with either autosomal dominant or autosomal recessive retinitis pigmentosa (PMID: 11527933, 19933189, 29425069, 30027431, 33681214). Therefore, variants that disrupt this region are expected to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
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Retinal dystrophy Pathogenic:2
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Retinitis pigmentosa 1 Pathogenic:1
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Retinitis pigmentosa Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at