rs121908456
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1PP5
The NM_022336.4(EDAR):c.1060G>T(p.Glu354Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
EDAR
NM_022336.4 stop_gained
NM_022336.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.57
Genes affected
EDAR (HGNC:2895): (ectodysplasin A receptor) This gene encodes a member of the tumor necrosis factor receptor family. The encoded transmembrane protein is a receptor for the soluble ligand ectodysplasin A, and can activate the nuclear factor-kappaB, JNK, and caspase-independent cell death pathways. It is required for the development of hair, teeth, and other ectodermal derivatives. Mutations in this gene result in autosomal dominant and recessive forms of hypohidrotic ectodermal dysplasia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 45 pathogenic variants in the truncated region.
PP5
?
Variant 2-108897194-C-A is Pathogenic according to our data. Variant chr2-108897194-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 5857.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-108897194-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDAR | NM_022336.4 | c.1060G>T | p.Glu354Ter | stop_gained | 12/12 | ENST00000258443.7 | |
EDAR | XM_006712204.2 | c.1156G>T | p.Glu386Ter | stop_gained | 11/11 | ||
RANBP2 | XM_047445367.1 | c.8370+124148C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDAR | ENST00000258443.7 | c.1060G>T | p.Glu354Ter | stop_gained | 12/12 | 1 | NM_022336.4 | P1 | |
EDAR | ENST00000376651.1 | c.1156G>T | p.Glu386Ter | stop_gained | 11/11 | 2 | |||
EDAR | ENST00000409271.5 | c.1156G>T | p.Glu386Ter | stop_gained | 12/12 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461508Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0AN XY: 727022
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1461508
Hom.:
Cov.:
39
AF XY:
AC XY:
0
AN XY:
727022
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Ectodermal dysplasia 10a, hypohidrotic/hair/tooth type, autosomal dominant Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2008 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A
Vest4
GERP RS
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