rs587781234
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PP4PS4_SupportingPM6_StrongPM2_Supporting
This summary comes from the ClinGen Evidence Repository: The p.Ser582del variant in UBE3A is absent from gnomAD (PM2_Supporting). The p.Ser582del variant in UBE3A has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with Angelman syndrome (PMID 25212744, internal database) (PM6_Strong). The p.Ser582del variant has been observed in at least 1 other individual with Angelman syndrome (PMID 25212744) (PS4_Supporting). The p.Ser582del variant in UBE3A has been reported in an individual with a clinical phenotype suggestive of Angelman syndrome (PMID 25212744) (PP4). In summary, the p.Ser582del variant in UBE3A is classified as likely pathogenic for Angelman syndrome based on the ACMG/AMP criteria (PM2_supporting, PM6_strong, PS4_supporting, PP4). LINK:https://erepo.genome.network/evrepo/ui/classification/CA333369/MONDO:0007113/016
Frequency
Consequence
NM_130839.5 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Angelman syndrome Pathogenic:4
Likely pathogenic, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Mar 26, 2021 | The p.Ser582del variant in UBE3A is absent from gnomAD (PM2_Supporting). The p.Ser582del variant in UBE3A has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with Angelman syndrome (PMID 25212744, internal database) (PM6_Strong). The p.Ser582del variant has been observed in at least 1 other individual with Angelman syndrome (PMID 25212744) (PS4_Supporting). The p.Ser582del variant in UBE3A has been reported in an individual with a clinical phenotype suggestive of Angelman syndrome (PMID 25212744) (PP4). In summary, the p.Ser582del variant in UBE3A is classified as likely pathogenic for Angelman syndrome based on the ACMG/AMP criteria (PM2_supporting, PM6_strong, PS4_supporting, PP4). - |
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 27, 2019 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Baylor Genetics | Feb 14, 2014 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 20, 2019 | Experimental studies and prediction algorithms are not available or were not evaluated for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has been observed to be de novo in individuals with clinical features of Angelman syndrome (PMID: 25212744, 25693842). ClinVar contains an entry for this variant (Variation ID: 155987). This variant is not present in population databases (ExAC no frequency). This variant, c.1745_1747del, results in the deletion of 1 amino acid(s) of the UBE3A protein (p.Ser582del), but otherwise preserves the integrity of the reading frame. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at