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
  • No CSPEC related information was provided by the message!
  • See Evidence submitted by expert panel for details.

Variant: NM_130839.5(UBE3A):c.2563_2568del (p.Leu855_Lys856del)

CA279164

217365 (ClinVar)

Gene: UBE3A
Condition: Angelman syndrome
Inheritance Mode: Autosomal dominant inheritance (with paternal imprinting (HP:0012274))
Link to MONDO
UUID: 46216cc0-af0a-465e-a1b0-ee31dfddaf68

HGVS expressions

NM_130839.5:c.2563_2568del
NM_130839.5(UBE3A):c.2563_2568del (p.Leu855_Lys856del)
NC_000015.10:g.25339191_25339196del
CM000677.2:g.25339191_25339196del
NC_000015.9:g.25584338_25584343del
CM000677.1:g.25584338_25584343del
NC_000015.8:g.23135431_23135436del
NG_009268.1:g.104789_104794del
ENST00000438097.6:c.2503_2508del
ENST00000635914.1:c.*888_*893del
ENST00000636667.1:c.100_105del
ENST00000637886.1:c.2563_2568del
ENST00000638011.1:c.2503_2508del
ENST00000638155.1:c.2503_2508del
ENST00000648336.2:c.2563_2568del
ENST00000649550.1:c.2503_2508del
ENST00000650110.1:c.2572_2577del
ENST00000675177.1:c.2386_2391del
ENST00000232165.7:c.2503_2508del
ENST00000397954.6:c.2572_2577del
ENST00000428984.6:c.2503_2508del
ENST00000438097.5:c.2503_2508del
ENST00000566215.5:c.2503_2508del
ENST00000604860.3:n.514_519del
ENST00000614096.4:c.2563_2568del
ENST00000626176.2:n.374_379del
ENST00000630424.2:c.2503_2508del
NM_000462.3:c.2572_2577del
NM_130838.1:c.2503_2508del
NM_130839.2:c.2563_2568del
NM_000462.5:c.2572_2577del
NM_001354505.1:c.2563_2568del
NM_001354506.1:c.2503_2508del
NM_001354507.1:c.2503_2508del
NM_001354508.1:c.2503_2508del
NM_001354509.1:c.2503_2508del
NM_001354511.1:c.2503_2508del
NM_001354512.1:c.2503_2508del
NM_001354513.1:c.2503_2508del
NM_001354523.1:c.2503_2508del
NM_001354526.1:c.2503_2508del
NM_001354538.1:c.2563_2568del
NM_001354539.1:c.2503_2508del
NM_001354540.1:c.2503_2508del
NM_001354541.1:c.2503_2508del
NM_001354542.1:c.2503_2508del
NM_001354543.1:c.2503_2508del
NM_001354544.1:c.2503_2508del
NM_001354545.1:c.2407_2412del
NM_001354546.1:c.2386_2391del
NM_001354547.1:c.2347_2352del
NM_001354548.1:c.2347_2352del
NM_001354549.1:c.2338_2343del
NM_001354550.1:c.1312_1317del
NM_001354551.1:c.1252_1257del
NM_130838.3:c.2503_2508del
NM_130839.4:c.2563_2568del
NR_146177.1:n.18393-52405_18393-52400del
NR_148916.1:n.3107_3112del
NM_001354506.2:c.2503_2508del
NM_001354507.2:c.2503_2508del
NM_001354508.2:c.2503_2508del
NM_001354509.2:c.2503_2508del
NM_001354511.2:c.2503_2508del
NM_001354512.2:c.2503_2508del
NM_001354513.2:c.2503_2508del
NM_001354523.2:c.2503_2508del
NM_001354538.2:c.2563_2568del
NM_001354539.2:c.2503_2508del
NM_001354540.2:c.2503_2508del
NM_001354541.2:c.2503_2508del
NM_001354542.2:c.2503_2508del
NM_001354543.2:c.2503_2508del
NM_001354544.2:c.2503_2508del
NM_001354545.2:c.2407_2412del
NM_001354546.2:c.2386_2391del
NM_001354547.2:c.2347_2352del
NM_001354548.2:c.2347_2352del
NM_001354549.2:c.2338_2343del
NM_001354550.2:c.1312_1317del
NM_001354551.2:c.1252_1257del
NM_001374461.1:c.2503_2508del
NM_130838.4:c.2503_2508del
NR_148916.2:n.3075_3080del

Pathogenic

Met criteria codes 5
PM4_Supporting PM2_Supporting PS4 PS2_Very Strong PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The c.2503_2508del p.(Leu835_Lys836del) variant in UBE3A (NM_130838.2) is absent from gnomAD (PM2_supporting). The p.(Leu835_Lys836del) variant has been observed in at least 5 individuals with a diagnosis of Angelman syndrome or a neurodevelopmental phenotype consistent with UBE3A-related disease (PMID 24796722; ClinVar SCV000829845.4, SCV000491076.2, SCV000332262.4) (PS4, PP4), where it has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in at least 3 of these individuals (ClinVar SCV000491076.2, SCV000829845.4, SCV000332262.4) (PS2_Very strong). The p.(Leu835_Lys836del) variant causes a change in the length of 2 amino acids in the protein due to an in-frame deletion or insertion in a non-repeat region of UBE3A (PM4_supporting). In summary, the c.2503_2508del p.(Leu835_Lys836del) variant in UBE3A is classified as Pathogenic for Angelman syndrome based on the ACMG/AMP criteria (PS2_very strong, PS4_strong, PP4, PM2_supporting, PM4_supporting).
Met criteria codes
PM4_Supporting
The p.Leu835_Lys836del variant causes a change in the length of 2 amino acids in the protein due to an in-frame deletion or insertion in a non-repeat region of UBE3A (PM4_supporting).
PM2_Supporting
The p.Leu835_Lys836del variant in UBE3A is absent from gnomAD (PM2_supporting).
PS4
The p.Leu835_Lys836del variant has been observed in at least 5 individuals with a diagnosis of Angelman syndrome or a neurodevelopmental phenotype consistent with UBE3A-related disease (PMID 24796722; ClinVar SCV000829845.4, SCV000491076.2, SCV000332262.4) (PS4).
PS2_Very Strong
The p.Leu835_Lys836del variant in UBE3A has been reported as a de novo occurrence (biological parentage both confirmed and unconfirmed) in at least 3 individuals with Angleman syndrome (ClinVar SCV000491076.2, SCV000829845.4, SCV000332262.4) (PS2_Very strong).
PP4
The p.Leu835_Lys836del variant in UBE3A has been reported in individuals with a clinical phenotype suggestive of Angelman syndrome (PMID 24796722, ClinVar SCV000829845.4) (PP4).
Approved on: 2022-06-30
Published on: 2022-06-30
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.