Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_130839.5(UBE3A):c.2563C>T (p.Leu855Phe)

CA294630

156620 (ClinVar)

Gene: UBE3A (HGNC:7337)
Condition: Angelman syndrome (MONDO:0007113)
Inheritance Mode: Autosomal dominant inheritance (with paternal imprinting (HP:0012274))
UUID: 0b0cd308-4e86-4727-9fb9-c9120a58828c
Approved on: 2026-08-24
Published on: 2026-10-23

HGVS expressions

NM_130839.5:c.2563C>T
NM_130839.5(UBE3A):c.2563C>T (p.Leu855Phe)
NC_000015.10:g.25339193G>A
CM000677.2:g.25339193G>A
NC_000015.9:g.25584340G>A
CM000677.1:g.25584340G>A
NC_000015.8:g.23135433G>A
NG_009268.1:g.104789C>T
ENST00000438097.6:c.2503C>T
ENST00000635914.1:c.*888C>T
ENST00000636667.1:c.100C>T
ENST00000637886.1:c.2563C>T
ENST00000638011.1:c.2503C>T
ENST00000638155.1:c.2503C>T
ENST00000648336.2:c.2563C>T
ENST00000649550.1:c.2503C>T
ENST00000650110.1:c.2572C>T
ENST00000675177.1:c.2386C>T
ENST00000232165.7:c.2503C>T
ENST00000397954.6:c.2572C>T
ENST00000428984.6:c.2503C>T
ENST00000438097.5:c.2503C>T
ENST00000566215.5:c.2503C>T
ENST00000604860.3:c.514C>T
ENST00000614096.4:c.2563C>T
ENST00000626176.2:c.374C>T
ENST00000630424.2:c.2503C>T
NM_000462.3:c.2572C>T
NM_130838.1:c.2503C>T
NM_130839.2:c.2563C>T
NM_000462.5:c.2572C>T
NM_001354505.1:c.2563C>T
NM_001354506.1:c.2503C>T
NM_001354507.1:c.2503C>T
NM_001354508.1:c.2503C>T
NM_001354509.1:c.2503C>T
NM_001354511.1:c.2503C>T
NM_001354512.1:c.2503C>T
NM_001354513.1:c.2503C>T
NM_001354523.1:c.2503C>T
NM_001354526.1:c.2503C>T
NM_001354538.1:c.2563C>T
NM_001354539.1:c.2503C>T
NM_001354540.1:c.2503C>T
NM_001354541.1:c.2503C>T
NM_001354542.1:c.2503C>T
NM_001354543.1:c.2503C>T
NM_001354544.1:c.2503C>T
NM_001354545.1:c.2407C>T
NM_001354546.1:c.2386C>T
NM_001354547.1:c.2347C>T
NM_001354548.1:c.2347C>T
NM_001354549.1:c.2338C>T
NM_001354550.1:c.1312C>T
NM_001354551.1:c.1252C>T
NM_130838.3:c.2503C>T
NM_130839.4:c.2563C>T
NR_146177.1:n.18393-52403G>A
NR_148916.1:n.3107C>T
NM_001354506.2:c.2503C>T
NM_001354507.2:c.2503C>T
NM_001354508.2:c.2503C>T
NM_001354509.2:c.2503C>T
NM_001354511.2:c.2503C>T
NM_001354512.2:c.2503C>T
NM_001354513.2:c.2503C>T
NM_001354523.2:c.2503C>T
NM_001354538.2:c.2563C>T
NM_001354539.2:c.2503C>T
NM_001354540.2:c.2503C>T
NM_001354541.2:c.2503C>T
NM_001354542.2:c.2503C>T
NM_001354543.2:c.2503C>T
NM_001354544.2:c.2503C>T
NM_001354545.2:c.2407C>T
NM_001354546.2:c.2386C>T
NM_001354547.2:c.2347C>T
NM_001354548.2:c.2347C>T
NM_001354549.2:c.2338C>T
NM_001354550.2:c.1312C>T
NM_001354551.2:c.1252C>T
NM_001374461.1:c.2503C>T
NM_130838.4:c.2503C>T
NR_148916.2:n.3075C>T
More

Likely Pathogenic

Met criteria codes 5
PS4_Supporting PP4 PP3 PM2_Supporting PP1_Moderate

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for UBE3A Version 7.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Leu835Phe variant in UBE3A (NM_130838.4) has been reported in an individual with a clinical phenotype suggestive of Angelman syndrome (internal database - University of Chicago Genetic Services Laboratories) (PP4). The variant has been reported to segregate in three informative meioses (internal database - University of Chicago Genetic Services Laboratories) (PP1_Moderate). The p.Leu835Phe variant has been observed in at least 1 other affected individual (internal database - GeneDx) (PS4_Supporting). The p.Leu835Phe variant in UBE3A is absent from gnomAD v4.1 (PM2_Supporting). Computational prediction analysis tools suggest a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Leu835Phe variant in UBE3A is classified as Likely Pathogenic for Angelman syndrome based on the ACMG/AMP criteria (PP1_Moderate, PS4_Supporting, PM2_Supporting, PP3, PP4). (UBE3A Specifications v7.0; curation approved on 8/24/2026)
Met criteria codes
PS4_Supporting
The p.Leu835Phe variant has been observed in at least 1 other affected individual (internal database - GeneDx) (PS4_Supporting).
PP4
The p.Leu835Phe variant in UBE3A has been reported in an individual with a clinical phenotype suggestive of Angelman syndrome (internal database - University of Chicago Genetic Services Laboratories) (PP4).
PP3
Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).
PM2_Supporting
The p.Leu835Phe variant in UBE3A is absent from gnomAD v4.1 (PM2_Supporting).
PP1_Moderate
The variant has been reported to segregate in three informative meioses (internal database - University of Chicago Genetic Services Laboratories) (PP1_Moderate).
Curation History
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