Submissions for variant NM_130839.5(UBE3A):c.815A>G (p.Asn272Ser)

gnomAD frequency: 0.00009  dbSNP: rs139928148

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV000144351	SCV002569931	benign	Angelman syndrome	2022-08-25	reviewed by expert panel	curation	The allele frequency of the p.Asn272Ser variant in UBE3A is 0.013% in European (Non-Finnish) sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Asn272Ser variant is observed in at least 4 unaffected individuals (internal database) (BS2). Computational analysis prediction tools suggest that the p.Asn272Ser variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Asn272Ser variant in UBE3A is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP4).
Genetic Services Laboratory, University of Chicago	RCV000144351	SCV000195381	uncertain significance	Angelman syndrome	2013-02-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001719911	SCV000616987	likely benign	not provided	2019-11-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000144351	SCV000754752	likely benign	Angelman syndrome	2024-01-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000144351	SCV000896438	uncertain significance	Angelman syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002512558	SCV003530193	likely benign	Inborn genetic diseases	2022-03-02	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Baylor Genetics	RCV000144351	SCV000188528	uncertain significance	Angelman syndrome	2014-02-14	no assertion criteria provided	clinical testing	possible diagnosis of Angelman syndrome
PreventionGenetics, part of Exact Sciences	RCV003945159	SCV004765469	likely benign	UBE3A-related disorder	2020-06-22	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).