13-48459831-C-T
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3PP5_Moderate
The NM_000321.3(RB1):c.2104C>T(p.Gln702Ter) variant causes a stop gained, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000321.3 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RB1 | NM_000321.3 | c.2104C>T | p.Gln702Ter | stop_gained, splice_region_variant | 20/27 | ENST00000267163.6 | |
RB1 | NM_001407165.1 | c.2104C>T | p.Gln702Ter | stop_gained, splice_region_variant | 20/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RB1 | ENST00000267163.6 | c.2104C>T | p.Gln702Ter | stop_gained, splice_region_variant | 20/27 | 1 | NM_000321.3 | P1 | |
RB1 | ENST00000650461.1 | c.2104C>T | p.Gln702Ter | stop_gained, splice_region_variant | 20/27 | ||||
RB1 | ENST00000643064.1 | c.194+78388C>T | intron_variant |
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD4 exome Cov.: 34
GnomAD4 genome Cov.: 30
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2013 | The p.Q702Xpathogenic mutation (also known as c.2104C>T), located in coding exon 20 of theRB1gene, results from a C to T substitution at nucleotide position 2104. This changes the glutamine at codon 702 to a stop codon within exon 20. ​This mutation was described in a 13-year-old patient with bilateral retinoblastoma (Barbosa RH et al. Invest Ophthalmol Vis Sci. 2013;54(5):3184-94). In addition to the clinical data presented in the literature, and since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at