rs797045087
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_145861.4(EDARADD):c.299_300insAAC(p.Cys100delinsTerThr) variant causes a stop gained, disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_145861.4 stop_gained, disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EDARADD | NM_145861.4 | c.299_300insAAC | p.Cys100delinsTerThr | stop_gained, disruptive_inframe_insertion | Exon 6 of 6 | ENST00000334232.9 | NP_665860.2 | |
EDARADD | NM_080738.5 | c.269_270insAAC | p.Cys90delinsTerThr | stop_gained, disruptive_inframe_insertion | Exon 6 of 6 | NP_542776.1 | ||
EDARADD | NM_001422628.1 | c.233_234insAAC | p.Cys78delinsTerThr | stop_gained, disruptive_inframe_insertion | Exon 8 of 8 | NP_001409557.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Cys100X variant in EDARADD has not been previously reported in individuals with disease and data from large population studies is insufficient to assess the frequency of the variant. This variant is an insertion of 3 bases at position c.299 and is expected to impact the protein by introducing a premature termination codon at position 100. This alteration occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Truncating and loss-of-function variants have not been established as a mechanism of disease in EDARADD. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Cys100X variant is uncertain. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at