rs397516674
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_001399.5(EDA):c.793G>A(p.Asp265Asn) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D265G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001399.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDA | NM_001399.5 | c.793G>A | p.Asp265Asn | missense_variant, splice_region_variant | 6/8 | ENST00000374552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDA | ENST00000374552.9 | c.793G>A | p.Asp265Asn | missense_variant, splice_region_variant | 6/8 | 1 | NM_001399.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 20, 2011 | Variant classified as Uncertain Significance - Favor Pathogenic. The Asp265Asn v ariant in EDA has not been reported in the literature nor previously identified by our laboratory. Aspartic acid (Asp) at position 265 is conserved across evol utionarily distant species, suggesting that a change to the amino acid may not b e tolerated. In addition, two computational analyses (PolyPhen2 and SIFT) sugge st that the change to asparagine (Asn) at this position may impact the protein. Furthermore, this variant is located near the conserved splice sequence and spl ice predictor programs also suggest that this variant may impact the protein spl icing. However, the accuracy of these predicative tools is unknown and therefor e, not predictive enough to assume pathogenicity. Without further information, such as control studies, functional analyses, or segregation data, the clinical significance of this variant cannot be determined at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at