X-100296786-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001184880.2(PCDH19):c.2938C>T(p.Arg980Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00131 in 1,209,314 control chromosomes in the GnomAD database, including 21 homozygotes. There are 488 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R980H) has been classified as Likely benign.
Frequency
Consequence
NM_001184880.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH19 | NM_001184880.2 | c.2938C>T | p.Arg980Cys | missense_variant | 6/6 | ENST00000373034.8 | |
PCDH19 | NM_001105243.2 | c.2797C>T | p.Arg933Cys | missense_variant | 5/5 | ||
PCDH19 | NM_020766.3 | c.2794C>T | p.Arg932Cys | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH19 | ENST00000373034.8 | c.2938C>T | p.Arg980Cys | missense_variant | 6/6 | 1 | NM_001184880.2 | A1 | |
PCDH19 | ENST00000255531.8 | c.2797C>T | p.Arg933Cys | missense_variant | 5/5 | 1 | P5 | ||
PCDH19 | ENST00000420881.6 | c.2794C>T | p.Arg932Cys | missense_variant | 5/5 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00204 AC: 228AN: 111790Hom.: 3 Cov.: 22 AF XY: 0.00233 AC XY: 79AN XY: 33946
GnomAD3 exomes AF: 0.00479 AC: 870AN: 181478Hom.: 22 AF XY: 0.00405 AC XY: 273AN XY: 67446
GnomAD4 exome AF: 0.00124 AC: 1359AN: 1097470Hom.: 18 Cov.: 30 AF XY: 0.00113 AC XY: 409AN XY: 362840
GnomAD4 genome AF: 0.00204 AC: 228AN: 111844Hom.: 3 Cov.: 22 AF XY: 0.00232 AC XY: 79AN XY: 34010
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 27, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 17, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 27, 2014 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 18, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Developmental and epileptic encephalopathy, 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at