chrX-100296269-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001184880.2(PCDH19):c.*8T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000566 in 1,180,965 control chromosomes in the GnomAD database, including 3 homozygotes. There are 174 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0028 ( 0 hom., 89 hem., cov: 23)
Exomes 𝑓: 0.00033 ( 3 hom. 85 hem. )
Consequence
PCDH19
NM_001184880.2 3_prime_UTR
NM_001184880.2 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0850
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant X-100296269-A-G is Benign according to our data. Variant chrX-100296269-A-G is described in ClinVar as [Benign]. Clinvar id is 138595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-100296269-A-G is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00283 (317/112102) while in subpopulation AFR AF= 0.0095 (293/30854). AF 95% confidence interval is 0.0086. There are 0 homozygotes in gnomad4. There are 89 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd at 89 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCDH19 | NM_001184880.2 | c.*8T>C | 3_prime_UTR_variant | 6/6 | ENST00000373034.8 | ||
PCDH19 | NM_001105243.2 | c.*8T>C | 3_prime_UTR_variant | 5/5 | |||
PCDH19 | NM_020766.3 | c.*8T>C | 3_prime_UTR_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH19 | ENST00000373034.8 | c.*8T>C | 3_prime_UTR_variant | 6/6 | 1 | NM_001184880.2 | A1 | ||
PCDH19 | ENST00000255531.8 | c.*8T>C | 3_prime_UTR_variant | 5/5 | 1 | P5 | |||
PCDH19 | ENST00000420881.6 | c.*8T>C | 3_prime_UTR_variant | 5/5 | 1 | A1 | |||
PCDH19 | ENST00000464981.1 | c.*8T>C | 3_prime_UTR_variant, NMD_transcript_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00283 AC: 317AN: 112050Hom.: 0 Cov.: 23 AF XY: 0.00260 AC XY: 89AN XY: 34218
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GnomAD3 exomes AF: 0.000876 AC: 159AN: 181466Hom.: 1 AF XY: 0.000638 AC XY: 43AN XY: 67420
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GnomAD4 exome AF: 0.000329 AC: 352AN: 1068863Hom.: 3 Cov.: 26 AF XY: 0.000251 AC XY: 85AN XY: 338411
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 22, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 16, 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. - |
Computational scores
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Name
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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