rs368963363
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001184880.2(PCDH19):c.888C>T(p.Gly296=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,211,236 control chromosomes in the GnomAD database, including 1 homozygotes. There are 150 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00017 ( 0 hom., 10 hem., cov: 25)
Exomes 𝑓: 0.00024 ( 1 hom. 140 hem. )
Consequence
PCDH19
NM_001184880.2 synonymous
NM_001184880.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.466
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant X-100407710-G-A is Benign according to our data. Variant chrX-100407710-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 138598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.466 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000168 (19/113013) while in subpopulation SAS AF= 0.00473 (13/2748). AF 95% confidence interval is 0.0028. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 10 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH19 | NM_001184880.2 | c.888C>T | p.Gly296= | synonymous_variant | 1/6 | ENST00000373034.8 | |
PCDH19 | NM_001105243.2 | c.888C>T | p.Gly296= | synonymous_variant | 1/5 | ||
PCDH19 | NM_020766.3 | c.888C>T | p.Gly296= | synonymous_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH19 | ENST00000373034.8 | c.888C>T | p.Gly296= | synonymous_variant | 1/6 | 1 | NM_001184880.2 | A1 | |
PCDH19 | ENST00000255531.8 | c.888C>T | p.Gly296= | synonymous_variant | 1/5 | 1 | P5 | ||
PCDH19 | ENST00000420881.6 | c.888C>T | p.Gly296= | synonymous_variant | 1/5 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000168 AC: 19AN: 112962Hom.: 0 Cov.: 25 AF XY: 0.000285 AC XY: 10AN XY: 35102
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GnomAD3 exomes AF: 0.000529 AC: 96AN: 181633Hom.: 0 AF XY: 0.000726 AC XY: 49AN XY: 67501
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GnomAD4 exome AF: 0.000236 AC: 259AN: 1098223Hom.: 1 Cov.: 33 AF XY: 0.000385 AC XY: 140AN XY: 363581
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GnomAD4 genome ? AF: 0.000168 AC: 19AN: 113013Hom.: 0 Cov.: 25 AF XY: 0.000284 AC XY: 10AN XY: 35163
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 17, 2014 | 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 | Apr 14, 2017 | 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. - |
Developmental and epileptic encephalopathy, 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at