rs748581653
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001184880.2(PCDH19):c.2873G>A(p.Arg958Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,206,546 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 82 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 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. R958W) has been classified as Uncertain significance.
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.2873G>A | p.Arg958Gln | missense_variant | 6/6 | ENST00000373034.8 | |
PCDH19 | NM_001105243.2 | c.2732G>A | p.Arg911Gln | missense_variant | 5/5 | ||
PCDH19 | NM_020766.3 | c.2729G>A | p.Arg910Gln | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH19 | ENST00000373034.8 | c.2873G>A | p.Arg958Gln | missense_variant | 6/6 | 1 | NM_001184880.2 | A1 | |
PCDH19 | ENST00000255531.8 | c.2732G>A | p.Arg911Gln | missense_variant | 5/5 | 1 | P5 | ||
PCDH19 | ENST00000420881.6 | c.2729G>A | p.Arg910Gln | missense_variant | 5/5 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000117 AC: 13AN: 111282Hom.: 1 Cov.: 22 AF XY: 0.000149 AC XY: 5AN XY: 33480
GnomAD3 exomes AF: 0.000194 AC: 35AN: 180554Hom.: 0 AF XY: 0.000284 AC XY: 19AN XY: 66824
GnomAD4 exome AF: 0.000174 AC: 191AN: 1095210Hom.: 0 Cov.: 29 AF XY: 0.000214 AC XY: 77AN XY: 360638
GnomAD4 genome ? AF: 0.0000988 AC: 11AN: 111336Hom.: 0 Cov.: 22 AF XY: 0.000149 AC XY: 5AN XY: 33544
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 9 Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Sep 24, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 01, 2018 | 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 19, 2022 | This alteration is classified as likely 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. - |
PCDH19-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 18, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | PCDH19: BP4, BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at