rs1304917337
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001184880.2(PCDH19):āc.2391C>Gā(p.Asp797Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,208,242 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001184880.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH19 | NM_001184880.2 | c.2391C>G | p.Asp797Glu | missense_variant | 3/6 | ENST00000373034.8 | |
PCDH19 | NM_001105243.2 | c.2250C>G | p.Asp750Glu | missense_variant | 2/5 | ||
PCDH19 | NM_020766.3 | c.2250C>G | p.Asp750Glu | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH19 | ENST00000373034.8 | c.2391C>G | p.Asp797Glu | missense_variant | 3/6 | 1 | NM_001184880.2 | A1 | |
PCDH19 | ENST00000255531.8 | c.2250C>G | p.Asp750Glu | missense_variant | 2/5 | 1 | P5 | ||
PCDH19 | ENST00000420881.6 | c.2250C>G | p.Asp750Glu | missense_variant | 2/5 | 1 | A1 | ||
PCDH19 | ENST00000636150.1 | c.66-174C>G | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000892 AC: 1AN: 112066Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34218
GnomAD3 exomes AF: 0.00000550 AC: 1AN: 181658Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67496
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1096176Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 1AN XY: 361568
GnomAD4 genome ? AF: 0.00000892 AC: 1AN: 112066Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34218
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 12, 2023 | This variant has not been reported in the literature in individuals affected with PCDH19-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.001%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 797 of the PCDH19 protein (p.Asp797Glu). ClinVar contains an entry for this variant (Variation ID: 533847). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PCDH19 protein function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at