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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_130838.1(UBE3A):c.2304G>A (p.Trp768Ter)

CA325622

7967 (ClinVar)

Gene: UBE3A
Condition: Angelman syndrome
Inheritance Mode: Autosomal dominant inheritance (with paternal imprinting (HP:0012274))
Link to MONDO
UUID: e2d45216-51ac-4982-a42b-f9feed9273d8

HGVS expressions

NM_130838.1:c.2304G>A
NM_130838.1(UBE3A):c.2304G>A (p.Trp768Ter)
ENST00000438097.6:c.2304G>A
ENST00000635914.1:c.2304G>A
ENST00000636667.1:c.-100G>A
ENST00000637886.1:c.2364G>A
ENST00000638011.1:c.2304G>A
ENST00000638155.1:c.2304G>A
ENST00000648336.2:c.2364G>A
ENST00000649550.1:c.2304G>A
ENST00000650110.1:c.2373G>A
ENST00000675177.1:c.2187G>A
ENST00000675593.1:n.5060G>A
ENST00000232165.7:c.2304G>A
ENST00000397954.6:c.2373G>A
ENST00000428984.6:c.2304G>A
ENST00000438097.5:c.2304G>A
ENST00000566215.5:c.2304G>A
ENST00000604860.3:n.315G>A
ENST00000614096.4:c.2364G>A
ENST00000626176.2:n.175G>A
ENST00000630424.2:c.2304G>A
NM_000462.3:c.2373G>A
NM_130839.2:c.2364G>A
NM_000462.5:c.2373G>A
NM_001354505.1:c.2364G>A
NM_001354506.1:c.2304G>A
NM_001354507.1:c.2304G>A
NM_001354508.1:c.2304G>A
NM_001354509.1:c.2304G>A
NM_001354511.1:c.2304G>A
NM_001354512.1:c.2304G>A
NM_001354513.1:c.2304G>A
NM_001354523.1:c.2304G>A
NM_001354526.1:c.2304G>A
NM_001354538.1:c.2364G>A
NM_001354539.1:c.2304G>A
NM_001354540.1:c.2304G>A
NM_001354541.1:c.2304G>A
NM_001354542.1:c.2304G>A
NM_001354543.1:c.2304G>A
NM_001354544.1:c.2304G>A
NM_001354545.1:c.2208G>A
NM_001354546.1:c.2187G>A
NM_001354547.1:c.2148G>A
NM_001354548.1:c.2148G>A
NM_001354549.1:c.2139G>A
NM_001354550.1:c.1113G>A
NM_001354551.1:c.1053G>A
NM_130838.3:c.2304G>A
NM_130839.4:c.2364G>A
NR_146177.1:n.18393-51377C>T
NR_148916.1:n.2908G>A
NM_001354506.2:c.2304G>A
NM_001354507.2:c.2304G>A
NM_001354508.2:c.2304G>A
NM_001354509.2:c.2304G>A
NM_001354511.2:c.2304G>A
NM_001354512.2:c.2304G>A
NM_001354513.2:c.2304G>A
NM_001354523.2:c.2304G>A
NM_001354538.2:c.2364G>A
NM_001354539.2:c.2304G>A
NM_001354540.2:c.2304G>A
NM_001354541.2:c.2304G>A
NM_001354542.2:c.2304G>A
NM_001354543.2:c.2304G>A
NM_001354544.2:c.2304G>A
NM_001354545.2:c.2208G>A
NM_001354546.2:c.2187G>A
NM_001354547.2:c.2148G>A
NM_001354548.2:c.2148G>A
NM_001354549.2:c.2139G>A
NM_001354550.2:c.1113G>A
NM_001354551.2:c.1053G>A
NM_001374461.1:c.2304G>A
NM_130838.4:c.2304G>A
NM_130839.5:c.2364G>A
NR_148916.2:n.2876G>A
NC_000015.10:g.25340219C>T
CM000677.2:g.25340219C>T
NC_000015.9:g.25585366C>T
CM000677.1:g.25585366C>T
NC_000015.8:g.23136459C>T
NG_009268.1:g.103763G>A

Pathogenic

Met criteria codes 5
PM2_Supporting PS4_Supporting PVS1 PP4 PP1

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Trp768Ter variant in UBE3A is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The p.Trp768Ter variant in the UBE3A gene is absent from gnomAD (PM2_supporting). The p.Trp768Ter variant in UBE3A has been reported in an individual with a clinical phenotype suggestive of Angelman syndrome (PMID 9792887) (PP1). This variant has been observed in at least 1 other individuals with Angelman syndrome (PMID 29915382) (PS4_supporting). The variant has been reported to segregate in two informative meioses (PMID 9792887) (PP1). In summary, the p.Trp768Ter variant in UBE3A is classified as Pathogenic for Angelman syndrome based on the ACMG/AMP criteria (PVS1, PS4_supporting, PM2_supporting, PP1, PP4).
Met criteria codes
PM2_Supporting
The c.2304G>A (p.Trp768Ter) variant in the UBE3A gene is absent from gnomAD.
PS4_Supporting
The p.Trp768Ter variant in the UBE3A gene has been observed in at least 1 other individual with Angelman syndrome (PMID 29915382).
Study of one family with Angelman syndrome. UBE3A sequence analysis was performed on two siblings affected with Angelman syndrome and their unaffected mother, following negative methylation analysis. This variant was identified in a heterozygous state in both affected children and their unaffected mother. PubMed:9792887
Study of 170 patients with ataxia and unknown etiology, tested using a targeted exome approach. Variant was identified in one patient with ataxia, spasticity, tremors, moderate global DD, gastrointestinal reflux. PubMed:29915382
PVS1
The p.Trp768Ter variant in UBE3A is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism.
PP4
This variant has been reported in patients with a clinical phenotype suggestive of Angelman syndrome
PP1
The variant has been reported to segregate in two affected family members with Angelman syndrome
Study of one family with Angelman syndrome. UBE3A sequence analysis was performed on two siblings affected with Angelman syndrome and their unaffected mother, following negative methylation analysis. This variant was identified in a heterozygous state in both affected children and their unaffected mother. PubMed:9792887
Approved on: 2021-03-01
Published on: 2021-05-05
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.