rs727504865
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001399.5(EDA):c.742-18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Consequence
EDA
NM_001399.5 intron
NM_001399.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.962
Genes affected
EDA (HGNC:3157): (ectodysplasin A) The protein encoded by this gene is a type II membrane protein that can be cleaved by furin to produce a secreted form. The encoded protein, which belongs to the tumor necrosis factor family, acts as a homotrimer and may be involved in cell-cell signaling during the development of ectodermal organs. Defects in this gene are a cause of ectodermal dysplasia, anhidrotic, which is also known as X-linked hypohidrotic ectodermal dysplasia. Several transcript variants encoding many different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EDA | NM_001399.5 | c.742-18T>G | intron_variant | ENST00000374552.9 | NP_001390.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EDA | ENST00000374552.9 | c.742-18T>G | intron_variant | 1 | NM_001399.5 | ENSP00000363680.4 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 05, 2013 | The 742-18T>G variant in EDA has not been previously reported in any other famil ies with X-linked hypohidrotic ectodermal dysplasia (XLHED) and is absent from l arge population studies. This variant is located in a 3' splice region and compu tational tools do not suggest an impact to splicing. However, this information i s not predictive enough to rule out pathogenicity. This variant was observed, or assumed by obligate carrier status, to segregate in four female family members with mild clinical features or laboratory test results consistent with XLHED. Al though there is no strong evidence that this particular variant is the causative variant, it is possible that the variant is a marker for a different linked but unidentified variant that is causative and co-segregating with disease. In summ ary, additional information is needed to fully assess the clinical significance of the 742-18T>G variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at