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]

Variant: NM_130839.5(UBE3A):c.1865A>G (p.Asn622Ser)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA333543

160214 (ClinVar)

Gene: UBE3A

Condition: Angelman syndrome

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

Link to MONDO

UUID: 6b1ccf7c-35e1-4ed6-98d0-59145ac754ef

Approved on: 2025-05-07

Published on: 2025-06-30

HGVS expressions

NM_130839.5:c.1865A>G

NM_130839.5(UBE3A):c.1865A>G (p.Asn622Ser)

NC_000015.10:g.25356785T>C

CM000677.2:g.25356785T>C

NC_000015.9:g.25601932T>C

CM000677.1:g.25601932T>C

NC_000015.8:g.23153025T>C

NG_009268.1:g.87197A>G

ENST00000438097.6:c.1805A>G

ENST00000625778.3:c.1805A>G

ENST00000635914.1:c.1805A>G

ENST00000637886.1:c.1865A>G

ENST00000638011.1:c.1805A>G

ENST00000638155.1:c.1805A>G

ENST00000648336.2:c.1865A>G

ENST00000649550.1:c.1805A>G

ENST00000650110.1:c.1874A>G

ENST00000675177.1:c.1688A>G

ENST00000675593.1:n.4561A>G

ENST00000232165.7:c.1805A>G

ENST00000397954.6:c.1874A>G

ENST00000428984.6:c.1805A>G

ENST00000438097.5:c.1805A>G

ENST00000566215.5:c.1805A>G

ENST00000614096.4:c.1865A>G

ENST00000625778.2:c.1805A>G

ENST00000630424.2:c.1805A>G

ENST00000631247.1:n.354A>G

NM_000462.3:c.1874A>G

NM_130838.1:c.1805A>G

NM_130839.2:c.1865A>G

NM_000462.5:c.1874A>G

NM_001354505.1:c.1865A>G

NM_001354506.1:c.1805A>G

NM_001354507.1:c.1805A>G

NM_001354508.1:c.1805A>G

NM_001354509.1:c.1805A>G

NM_001354511.1:c.1805A>G

NM_001354512.1:c.1805A>G

NM_001354513.1:c.1805A>G

NM_001354523.1:c.1805A>G

NM_001354526.1:c.1805A>G

NM_001354538.1:c.1865A>G

NM_001354539.1:c.1805A>G

NM_001354540.1:c.1805A>G

NM_001354541.1:c.1805A>G

NM_001354542.1:c.1805A>G

NM_001354543.1:c.1805A>G

NM_001354544.1:c.1805A>G

NM_001354545.1:c.1865A>G

NM_001354546.1:c.1688A>G

NM_001354547.1:c.1805A>G

NM_001354548.1:c.1805A>G

NM_001354549.1:c.1805A>G

NM_001354550.1:c.614A>G

NM_001354551.1:c.554A>G

NM_130838.3:c.1805A>G

NM_130839.4:c.1865A>G

NR_146177.1:n.18393-34811T>C

NR_148916.1:n.2409A>G

NM_001354506.2:c.1805A>G

NM_001354507.2:c.1805A>G

NM_001354508.2:c.1805A>G

NM_001354509.2:c.1805A>G

NM_001354511.2:c.1805A>G

NM_001354512.2:c.1805A>G

NM_001354513.2:c.1805A>G

NM_001354523.2:c.1805A>G

NM_001354538.2:c.1865A>G

NM_001354539.2:c.1805A>G

NM_001354540.2:c.1805A>G

NM_001354541.2:c.1805A>G

NM_001354542.2:c.1805A>G

NM_001354543.2:c.1805A>G

NM_001354544.2:c.1805A>G

NM_001354545.2:c.1865A>G

NM_001354546.2:c.1688A>G

NM_001354547.2:c.1805A>G

NM_001354548.2:c.1805A>G

NM_001354549.2:c.1805A>G

NM_001354550.2:c.614A>G

NM_001354551.2:c.554A>G

NM_001374461.1:c.1805A>G

NM_130838.4:c.1805A>G

NR_148916.2:n.2377A>G

Likely Pathogenic

PP3 PM6 PS4_Moderate PM2_Supporting

PP4 BP4

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for UBE3A Version 5.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The c.1805A>G p.(Asn602Ser) variant in UBE3A (NM_130838.2) is absent from gnomAD (PM2_supporting). The p.Asn602Ser variant has been observed in at least 4 individuals with a neurodevelopmental phenotype consistent with UBE3A-related disease (University of Chicago, Ambry Genetics and GeneDx Internal databases) (PS4_moderate), and has been reported as a de novo occurrence (biological parentage unconfirmed) in 1 of these individuals (PM6). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Asn602Ser variant in UBE3A is classified as likely pathogenic for Angelman syndrome based on the ACMG/AMP criteria (PM2_supporting, PS4_moderate, PM6, PP3). (UBE3A Specifications v.5.0; curation approved on [5/7/2025])

PP3

Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3).

PM6

The p.Asn602Ser variant in UBE3A has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with a neurodevelopmental phenotype consistent with UBE3A (ClinVar SCV000741231.2).

PS4_Moderate

The p.Asn602Ser variant has been observed in 4 individuals with a neurodevelopmental phenotype consistent with UBE3A-related disease (University of Chicago, Ambry Genetics and GeneDx Internal databases) (PS4_moderate).

PM2_Supporting

The p.Asn602Ser variant in UBE3A is absent from gnomAD v4.1 (PM2_supporting).

PP4

This variant has been identified in at least 3 patients from external laboratories however the clinical details provided for these patients is insufficient to apply PP4.

BP4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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