Evidence Repository - Clinical Genome Resources

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

Variant: NM_130838.1(UBE3A):c.2507_2510delAAGA (p.Lys836Argfs)

CA333552

160220 (ClinVar)

Gene: UBE3A

Condition: Angelman syndrome

Inheritance Mode: Autosomal dominant inheritance (with paternal imprinting (HP:0012274))

Link to MONDO

UUID: 02ad9f68-22f2-45f8-9ae7-9356fb754050

Approved on: 2021-03-26

Published on: 2021-05-17

HGVS expressions

NM_130838.1:c.2507_2510delAAGA

NM_130838.1:c.2507_2510del

NM_130838.1(UBE3A):c.2507_2510delAAGA (p.Lys836Argfs)

ENST00000438097.6:c.2507_2510del

ENST00000635914.1:c.*892_*895del

ENST00000636667.1:c.104_107del

ENST00000637886.1:c.2567_2570del

ENST00000638011.1:c.2507_2510del

ENST00000638155.1:c.2507_2510del

ENST00000648336.2:c.2567_2570del

ENST00000649550.1:c.2507_2510del

ENST00000650110.1:c.2576_2579del

ENST00000675177.1:c.2390_2393del

ENST00000232165.7:c.2507_2510del

ENST00000397954.6:c.2576_2579del

ENST00000428984.6:c.2507_2510del

ENST00000438097.5:c.2507_2510del

ENST00000566215.5:c.2507_2510del

ENST00000604860.3:n.518_521del

ENST00000614096.4:c.2567_2570del

ENST00000626176.2:n.378_381del

ENST00000630424.2:c.2507_2510del

NM_000462.3:c.2576_2579del

NM_130839.2:c.2567_2570del

NM_000462.5:c.2576_2579del

NM_001354505.1:c.2567_2570del

NM_001354506.1:c.2507_2510del

NM_001354507.1:c.2507_2510del

NM_001354508.1:c.2507_2510del

NM_001354509.1:c.2507_2510del

NM_001354511.1:c.2507_2510del

NM_001354512.1:c.2507_2510del

NM_001354513.1:c.2507_2510del

NM_001354523.1:c.2507_2510del

NM_001354526.1:c.2507_2510del

NM_001354538.1:c.2567_2570del

NM_001354539.1:c.2507_2510del

NM_001354540.1:c.2507_2510del

NM_001354541.1:c.2507_2510del

NM_001354542.1:c.2507_2510del

NM_001354543.1:c.2507_2510del

NM_001354544.1:c.2507_2510del

NM_001354545.1:c.2411_2414del

NM_001354546.1:c.2390_2393del

NM_001354547.1:c.2351_2354del

NM_001354548.1:c.2351_2354del

NM_001354549.1:c.2342_2345del

NM_001354550.1:c.1316_1319del

NM_001354551.1:c.1256_1259del

NM_130838.3:c.2507_2510del

NM_130839.4:c.2567_2570del

NR_146177.1:n.18393-52409_18393-52406del

NR_148916.1:n.3111_3114del

NM_001354506.2:c.2507_2510del

NM_001354507.2:c.2507_2510del

NM_001354508.2:c.2507_2510del

NM_001354509.2:c.2507_2510del

NM_001354511.2:c.2507_2510del

NM_001354512.2:c.2507_2510del

NM_001354513.2:c.2507_2510del

NM_001354523.2:c.2507_2510del

NM_001354538.2:c.2567_2570del

NM_001354539.2:c.2507_2510del

NM_001354540.2:c.2507_2510del

NM_001354541.2:c.2507_2510del

NM_001354542.2:c.2507_2510del

NM_001354543.2:c.2507_2510del

NM_001354544.2:c.2507_2510del

NM_001354545.2:c.2411_2414del

NM_001354546.2:c.2390_2393del

NM_001354547.2:c.2351_2354del

NM_001354548.2:c.2351_2354del

NM_001354549.2:c.2342_2345del

NM_001354550.2:c.1316_1319del

NM_001354551.2:c.1256_1259del

NM_001374461.1:c.2507_2510del

NM_130838.4:c.2507_2510del

NM_130839.5:c.2567_2570del

NR_148916.2:n.3079_3082del

NC_000015.10:g.25339187_25339190del

CM000677.2:g.25339187_25339190del

NC_000015.9:g.25584334_25584337del

CM000677.1:g.25584334_25584337del

NC_000015.8:g.23135427_23135430del

NG_009268.1:g.104793_104796del

Pathogenic

PVS1 PS4 PM6 PM2_Supporting

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Lys836Argfs variant in UBE3A is predicted to cause a premature stop codon that leads to a truncated 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). This variant has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with Angelman syndrome (PMID 9887341) (PM6). This variant has been observed in at least 4 other individuals with Angelman syndrome (PMID 9887341, 25212744, ClinVar) (PS4). The p.Lys836Argfs variant in UBE3A is absent from gnomAD (PM2_supporting). In summary, the p.Lys836Argfs variant in UBE3A is classified as Pathogenic for Angelman syndrome based on the ACMG/AMP criteria (PVS1, PS4, PM6, PM2_supporting).

PVS1

The p.(Lys836Argfs) 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.

PS4

The p.(Lys836Argfs) variant has been observed in at least 5 other individuals with Angelman syndrome (PMID 9887341, 25212744; ClinVar 160220)

PM6

The p.(Lys836Argfs) variant in UBE3A has been reported as an unconfirmed de novo occurrence in a individual with Angelman syndrome (PMID 9887341)

PM2_Supporting

The p.(Lys836Argfs) variant in the UBE3A gene is absent from gnomAD

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