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]
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Variant: NM_130838.1(UBE3A):c.2503C>T (p.Leu835Phe)

CA294630

156620 (ClinVar)

Gene: UBE3A
Condition: Angelman syndrome
Inheritance Mode: Autosomal dominant inheritance (with paternal imprinting (HP:0012274))
Link to MONDO
UUID: 0b0cd308-4e86-4727-9fb9-c9120a58828c
Approved on: 2021-03-26
Published on: 2021-05-17

HGVS expressions

NM_130838.1:c.2503C>T
NM_130838.1(UBE3A):c.2503C>T (p.Leu835Phe)
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:n.514C>T
ENST00000614096.4:c.2563C>T
ENST00000626176.2:n.374C>T
ENST00000630424.2:c.2503C>T
NM_000462.3:c.2572C>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
NM_130839.5:c.2563C>T
NR_148916.2:n.3075C>T

Likely Pathogenic

Met criteria codes 5
PP1_Moderate PS4_Supporting PM2_Supporting PP4 PP3

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Leu835Phe variant in UBE3A is absent from gnomAD (PM2_Supporting). The p.Leu835Phe variant has been observed in at least 1 other affected individual (PMID 29655203) (PS4_Supporting). The variant has been reported to segregate in three informative meioses (PP1_moderate). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). The p.Leu835Phe variant in UBE3A has been reported in an individual with a clinical phenotype suggestive of Angelman syndrome (PP4). In summary, the p.Leu835Phe variant in UBE3A is classified as likely pathogenic for Angelman syndrome based on the ACMG/AMP criteria (PM2_supporting, PS4_supporting, PP1_moderate, PP3, PP4).
Met criteria codes
PP1_Moderate
The variant has been reported to segregate in three informative meioses
PS4_Supporting
The p.Leu835Phe variant has been observed in at least 1 other affected individual (PMID 29655203)
Study of 8565 patients with epilepsy and neurodevelopmental disorders. Molecular test results for 70 genes known to cause epilepsy and neurodevelopmental disorders using next generation sequencing (NGS) and exon-level array comparative genomic hybridization were reviewed. This variant was found in one patient. PubMed:29655203
PM2_Supporting
The p.Leu835Phe variant in UBE3A is absent from gnomAD
PP4
The p.Leu835Phe variant in UBE3A has been reported in an individual with a clinical phenotype suggestive of Angelman syndrome
PP3
Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own
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