rs16983426
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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.3018C>T(p.Asp1006=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,209,196 control chromosomes in the GnomAD database, including 36 homozygotes. There are 841 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 21 hom., 388 hem., cov: 23)
Exomes 𝑓: 0.0016 ( 15 hom. 453 hem. )
Consequence
PCDH19
NM_001184880.2 synonymous
NM_001184880.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0540
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=-0.54).
BP6
?
Variant X-100296706-G-A is Benign according to our data. Variant chrX-100296706-G-A is described in ClinVar as [Benign]. Clinvar id is 138591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-100296706-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.054 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1449/111072) while in subpopulation AFR AF= 0.0429 (1305/30454). AF 95% confidence interval is 0.0409. There are 21 homozygotes in gnomad4. There are 388 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 21 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH19 | NM_001184880.2 | c.3018C>T | p.Asp1006= | synonymous_variant | 6/6 | ENST00000373034.8 | |
PCDH19 | NM_001105243.2 | c.2877C>T | p.Asp959= | synonymous_variant | 5/5 | ||
PCDH19 | NM_020766.3 | c.2874C>T | p.Asp958= | synonymous_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH19 | ENST00000373034.8 | c.3018C>T | p.Asp1006= | synonymous_variant | 6/6 | 1 | NM_001184880.2 | A1 | |
PCDH19 | ENST00000255531.8 | c.2877C>T | p.Asp959= | synonymous_variant | 5/5 | 1 | P5 | ||
PCDH19 | ENST00000420881.6 | c.2874C>T | p.Asp958= | synonymous_variant | 5/5 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0130 AC: 1444AN: 111018Hom.: 21 Cov.: 23 AF XY: 0.0116 AC XY: 387AN XY: 33236
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GnomAD3 exomes AF: 0.00433 AC: 786AN: 181532Hom.: 8 AF XY: 0.00311 AC XY: 210AN XY: 67492
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GnomAD4 exome AF: 0.00164 AC: 1804AN: 1098124Hom.: 15 Cov.: 31 AF XY: 0.00125 AC XY: 453AN XY: 363490
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GnomAD4 genome ? AF: 0.0130 AC: 1449AN: 111072Hom.: 21 Cov.: 23 AF XY: 0.0117 AC XY: 388AN XY: 33300
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 19, 2012 | 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
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 27, 2017 | - - |
Developmental and epileptic encephalopathy, 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at