rs863224650
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000264.5(PTCH1):c.1804C>T(p.Arg602Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R602R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000264.5 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 |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.1804C>T | p.Arg602Ter | stop_gained | 13/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.1801C>T | p.Arg601Ter | stop_gained | 13/24 | ENST00000437951.6 | |
LOC100507346 | NR_038982.1 | n.1794G>A | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.1804C>T | p.Arg602Ter | stop_gained | 13/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.1801C>T | p.Arg601Ter | stop_gained | 13/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Gorlin syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 19, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 428829). This variant is also known as c.1792C>T. This premature translational stop signal has been observed in individual(s) with clinical features of PTCH1-related conditions (PMID: 16906569; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg602*) in the PTCH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTCH1 are known to be pathogenic (PMID: 16301862, 16419085). - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 28, 2015 | The p.R602* pathogenic mutation (also known as c.1804C>T), located in coding exon 13 of the PTCH1 gene, results from a C to T substitution at nucleotide position 1804. This changes the amino acid from an arginine to a stop codon within coding exon 13. This mutation has been previously reported in a family affected with Gorlin syndrome (Wilson LC, Am. J. Med. Genet. A 2006 Dec; 140(23):2625-30). In addition to the clinical data presented in the literature, 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