ClinVar Genomic variation as it relates to human health
NM_130839.5(UBE3A):c.2344G>A (p.Val782Ile)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_130839.5(UBE3A):c.2344G>A (p.Val782Ile)
Variation ID: 156124 Accession: VCV000156124.12
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 15q11.2 15: 25354363 (GRCh38) [ NCBI UCSC ] 15: 25599510 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 4, 2014 May 1, 2024 Jun 30, 2022 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_130839.5:c.2344G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_570854.1:p.Val782Ile missense NM_000462.5:c.2353G>A NP_000453.2:p.Val785Ile missense NM_001354505.1:c.2344G>A NP_001341434.1:p.Val782Ile missense NM_001354506.2:c.2284G>A NP_001341435.1:p.Val762Ile missense NM_001354507.2:c.2284G>A NP_001341436.1:p.Val762Ile missense NM_001354508.2:c.2284G>A NP_001341437.1:p.Val762Ile missense NM_001354509.2:c.2284G>A NP_001341438.1:p.Val762Ile missense NM_001354511.2:c.2284G>A NP_001341440.1:p.Val762Ile missense NM_001354512.2:c.2284G>A NP_001341441.1:p.Val762Ile missense NM_001354513.2:c.2284G>A NP_001341442.1:p.Val762Ile missense NM_001354523.2:c.2284G>A NP_001341452.1:p.Val762Ile missense NM_001354526.1:c.2284G>A NP_001341455.1:p.Val762Ile missense NM_001354538.2:c.2344G>A NP_001341467.1:p.Val782Ile missense NM_001354539.2:c.2284G>A NP_001341468.1:p.Val762Ile missense NM_001354540.2:c.2284G>A NP_001341469.1:p.Val762Ile missense NM_001354541.2:c.2284G>A NP_001341470.1:p.Val762Ile missense NM_001354542.2:c.2284G>A NP_001341471.1:p.Val762Ile missense NM_001354543.2:c.2284G>A NP_001341472.1:p.Val762Ile missense NM_001354544.2:c.2284G>A NP_001341473.1:p.Val762Ile missense NM_001354545.2:c.2188G>A NP_001341474.1:p.Val730Ile missense NM_001354546.2:c.2167G>A NP_001341475.1:p.Val723Ile missense NM_001354547.2:c.2128G>A NP_001341476.1:p.Val710Ile missense NM_001354548.2:c.2128G>A NP_001341477.1:p.Val710Ile missense NM_001354549.2:c.2119G>A NP_001341478.1:p.Val707Ile missense NM_001354550.2:c.1093G>A NP_001341479.1:p.Val365Ile missense NM_001354551.2:c.1033G>A NP_001341480.1:p.Val345Ile missense NM_001374461.1:c.2284G>A NP_001361390.1:p.Val762Ile missense NM_130838.4:c.2284G>A NP_570853.1:p.Val762Ile missense NR_148916.2:n.2856G>A non-coding transcript variant NC_000015.10:g.25354363C>T NC_000015.9:g.25599510C>T NG_009268.1:g.89619G>A LRG_15:g.89619G>A LRG_15t1:c.2284G>A - Protein change
- V762I, V782I, V365I, V723I, V707I, V730I, V785I, V345I, V710I
- Other names
- p.V782I:GTT>ATT
- NM_130839.5(UBE3A):c.2344G>A
- p.Val782Ile
- Canonical SPDI
- NC_000015.10:25354362:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
UBE3A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
34 | 1202 | |
SNHG14 | - | - | GRCh38 | 4 | 1102 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Uncertain significance (3) |
reviewed by expert panel
|
Jun 30, 2022 | RCV000144327.7 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Jul 1, 2016 | RCV000147880.8 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jun 21, 2017 | RCV002444596.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Uncertain significance
(Jun 30, 2022)
|
reviewed by expert panel
Method: curation
|
Angelman syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel
Accession: SCV002540713.1
First in ClinVar: Jul 09, 2022 Last updated: Jul 09, 2022 |
Comment:
The c.2284G>A p.(Val762Ile) variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.004% in the African/African-American sub population (no criteria met). … (more)
The c.2284G>A p.(Val762Ile) variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.004% in the African/African-American sub population (no criteria met). The p.(Val762Ile) variant has been observed in at least 1 individual with a neurodevelopmental phenotype consistent with UBE3A-related disease (PMID 25212744), however the PS4 criteria cannot be applied due to the gnomAD frequency of this variant. Computational analysis prediction tools suggest that the p.(Val762Ile) variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the c.2284G>A p.(Val762Ile) variant in UBE3A is classified as a Variant of Uncertain Signficance based on the ACMG/AMP criteria (BP4). (less)
|
|
Likely benign
(May 08, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000195363.2
First in ClinVar: Nov 23, 2014 Last updated: Oct 05, 2015 |
|
|
Likely benign
(Jul 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000191058.6
First in ClinVar: Nov 01, 2014 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
Uncertain significance
(Dec 21, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Angelman syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000548105.5
First in ClinVar: Oct 04, 2014 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 762 of the UBE3A protein (p.Val762Ile). … (more)
This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 762 of the UBE3A protein (p.Val762Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of Angelman syndrome (PMID: 25212744). ClinVar contains an entry for this variant (Variation ID: 156124). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt UBE3A protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
Uncertain significance
(Jun 21, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002734721.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.V762I variant (also known as c.2284G>A), located in coding exon 8 of the UBE3A gene, results from a G to A substitution at nucleotide … (more)
The p.V762I variant (also known as c.2284G>A), located in coding exon 8 of the UBE3A gene, results from a G to A substitution at nucleotide position 2284. The valine at codon 762 is replaced by isoleucine, an amino acid with highly similar properties. This alteration has been detected in a proband from an Angelman syndrome cohort and in the proband's reportedly symptomatic maternal half-sibling; however, clinical details were limited (Sadikovic B et al. Hum. Mutat., 2014 Dec;35:1407-17). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
Uncertain significance
(Feb 14, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Angelman syndrome
Affected status: yes
Allele origin:
maternal,
germline
|
Baylor Genetics
Study: UBE3A Mutation Study
Accession: SCV000188504.1 First in ClinVar: Oct 04, 2014 Last updated: Oct 04, 2014
Comment:
Data collected from clinical UBE3A sequence analysis results
|
Comment:
possible diagnosis of Angelman syndrome
Observation 1:
Number of individuals with the variant: 3
Observation 2:
Number of individuals with the variant: 1
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Mutation Update for UBE3A variants in Angelman syndrome. | Sadikovic B | Human mutation | 2014 | PMID: 25212744 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/1dfb40bb-2608-4082-bd94-5398bca77095 | - | - | - | - |
Text-mined citations for rs587782910 ...
HelpRecord last updated May 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.