rs769967221
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001184880.2(PCDH19):c.1183C>T(p.Arg395Ter) 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. R395R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001184880.2 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 |
---|---|---|---|---|---|---|---|
PCDH19 | NM_001184880.2 | c.1183C>T | p.Arg395Ter | stop_gained | 1/6 | ENST00000373034.8 | |
PCDH19 | NM_001105243.2 | c.1183C>T | p.Arg395Ter | stop_gained | 1/5 | ||
PCDH19 | NM_020766.3 | c.1183C>T | p.Arg395Ter | stop_gained | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH19 | ENST00000373034.8 | c.1183C>T | p.Arg395Ter | stop_gained | 1/6 | 1 | NM_001184880.2 | A1 | |
PCDH19 | ENST00000255531.8 | c.1183C>T | p.Arg395Ter | stop_gained | 1/5 | 1 | P5 | ||
PCDH19 | ENST00000420881.6 | c.1183C>T | p.Arg395Ter | stop_gained | 1/5 | 1 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 25
GnomAD4 exome Cov.: 33
GnomAD4 genome ? Cov.: 25
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 9 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Dec 16, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 533856). This premature translational stop signal has been observed in individual(s) with clinical features of epilepsy (PMID: 22946748). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg395*) in the PCDH19 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCDH19 are known to be pathogenic (PMID: 21053371). - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at