X-100402718-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001184880.2(PCDH19):​c.2422A>C​(p.Thr808Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T808S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Consequence

PCDH19
NM_001184880.2 missense

Scores

2
5
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.96
Variant links:
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3342697).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCDH19NM_001184880.2 linkc.2422A>C p.Thr808Pro missense_variant Exon 3 of 6 ENST00000373034.8 NP_001171809.1 Q8TAB3-1
PCDH19NM_001105243.2 linkc.2281A>C p.Thr761Pro missense_variant Exon 2 of 5 NP_001098713.1 Q8TAB3-2B3KU71
PCDH19NM_020766.3 linkc.2281A>C p.Thr761Pro missense_variant Exon 2 of 5 NP_065817.2 Q8TAB3-3B3KU71

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCDH19ENST00000373034.8 linkc.2422A>C p.Thr808Pro missense_variant Exon 3 of 6 1 NM_001184880.2 ENSP00000362125.4 Q8TAB3-1
PCDH19ENST00000255531.8 linkc.2281A>C p.Thr761Pro missense_variant Exon 2 of 5 1 ENSP00000255531.7 Q8TAB3-2
PCDH19ENST00000420881.6 linkc.2281A>C p.Thr761Pro missense_variant Exon 2 of 5 1 ENSP00000400327.2 Q8TAB3-3
PCDH19ENST00000636150.1 linkc.66-143A>C intron_variant Intron 1 of 2 5 ENSP00000490463.1 A0A1B0GVC8

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.13
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.023
.;T;.
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.85
T;D;T
M_CAP
Pathogenic
0.36
D
MetaRNN
Benign
0.33
T;T;T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
0.34
.;N;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
0.030
N;N;N
REVEL
Benign
0.20
Sift
Benign
0.28
T;T;T
Sift4G
Benign
0.33
T;T;T
Polyphen
1.0, 0.047
.;D;B
Vest4
0.43
MutPred
0.45
.;Loss of sheet (P = 0.007);.;
MVP
0.89
MPC
1.6
ClinPred
0.73
D
GERP RS
5.6
Varity_R
0.48
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs111960928; hg19: chrX-99657716; API