rs1131691646
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001184880.2(PCDH19):c.1521del(p.Ile508SerfsTer61) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 24)
Consequence
PCDH19
NM_001184880.2 frameshift
NM_001184880.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.41
Genes affected
PCDH19 (HGNC:14270): (protocadherin 19) The protein encoded by this gene is a member of the delta-2 protocadherin subclass of the cadherin superfamily. The encoded protein is thought to be a calcium-dependent cell-adhesion protein that is primarily expressed in the brain. Mutations in this gene on human chromosome X are associated with sporadic infantile epileptic encephalopathy and to a female-restricted form of epilepsy (EFMR; also known as PCDH19RE). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-100407076-TG-T is Pathogenic according to our data. Variant chrX-100407076-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 429878.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-100407076-TG-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH19 | NM_001184880.2 | c.1521del | p.Ile508SerfsTer61 | frameshift_variant | 1/6 | ENST00000373034.8 | |
PCDH19 | NM_001105243.2 | c.1521del | p.Ile508SerfsTer61 | frameshift_variant | 1/5 | ||
PCDH19 | NM_020766.3 | c.1521del | p.Ile508SerfsTer61 | frameshift_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH19 | ENST00000373034.8 | c.1521del | p.Ile508SerfsTer61 | frameshift_variant | 1/6 | 1 | NM_001184880.2 | A1 | |
PCDH19 | ENST00000255531.8 | c.1521del | p.Ile508SerfsTer61 | frameshift_variant | 1/5 | 1 | P5 | ||
PCDH19 | ENST00000420881.6 | c.1521del | p.Ile508SerfsTer61 | frameshift_variant | 1/5 | 1 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2015 | The c.1521delC deletion in the PCDH19 gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. It was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although the c.1521delC variant has not been previously reported to our knowledge, many other frameshift variants downstream of this position have been reported in the Human Gene Mutation Database in association with PCDH19-related disorders (Stenson et al., 2014). We interpret the c.1521delC deletion as a pathogenic variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at