Frameshift variant predicted to result in protein truncation, as the last 63 amino acids are replaced with 6 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25212744, 35414530)
ClinVar Genomic variation as it relates to human health
NM_130839.5(UBE3A):c.2430_2433del (p.Asp810fs)
Germline
Classification
Help
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.
(4)
Help
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.
Pathogenic
4
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_130839.5(UBE3A):c.2430_2433del (p.Asp810fs)
Variation ID: 155976 Accession: VCV000155976.34
- Type and length
-
Microsatellite, 4 bp
- Location
-
Cytogenetic: 15q11.2 15: 25340150-25340153 (GRCh38) [ NCBI UCSC ] 15: 25585297-25585300 (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 Dec 22, 2024 May 11, 2022 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_130839.5:c.2430_2433del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_570854.1:p.Asp810fs frameshift NM_000462.5:c.2439_2442del NP_000453.2:p.Asp813fs frameshift NM_001354505.1:c.2430_2433del NP_001341434.1:p.Asp810fs frameshift NM_001354506.2:c.2370_2373del NP_001341435.1:p.Asp790fs frameshift NM_001354507.2:c.2370_2373del NP_001341436.1:p.Asp790fs frameshift NM_001354508.2:c.2370_2373del NP_001341437.1:p.Asp790fs frameshift NM_001354509.2:c.2370_2373del NP_001341438.1:p.Asp790fs frameshift NM_001354511.2:c.2370_2373del NP_001341440.1:p.Asp790fs frameshift NM_001354512.2:c.2370_2373del NP_001341441.1:p.Asp790fs frameshift NM_001354513.2:c.2370_2373del NP_001341442.1:p.Asp790fs frameshift NM_001354523.2:c.2370_2373del NP_001341452.1:p.Asp790fs frameshift NM_001354526.1:c.2370_2373del NP_001341455.1:p.Asp790fs frameshift NM_001354538.2:c.2430_2433del NP_001341467.1:p.Asp810fs frameshift NM_001354539.2:c.2370_2373del NP_001341468.1:p.Asp790fs frameshift NM_001354540.2:c.2370_2373del NP_001341469.1:p.Asp790fs frameshift NM_001354541.2:c.2370_2373del NP_001341470.1:p.Asp790fs frameshift NM_001354542.2:c.2370_2373del NP_001341471.1:p.Asp790fs frameshift NM_001354543.2:c.2370_2373del NP_001341472.1:p.Asp790fs frameshift NM_001354544.2:c.2370_2373del NP_001341473.1:p.Asp790fs frameshift NM_001354545.2:c.2274_2277del NP_001341474.1:p.Asp758fs frameshift NM_001354546.2:c.2253_2256del NP_001341475.1:p.Asp751fs frameshift NM_001354547.2:c.2214_2217del NP_001341476.1:p.Asp738fs frameshift NM_001354548.2:c.2214_2217del NP_001341477.1:p.Asp738fs frameshift NM_001354549.2:c.2205_2208del NP_001341478.1:p.Asp735fs frameshift NM_001354550.2:c.1179_1182del NP_001341479.1:p.Asp393fs frameshift NM_001354551.2:c.1119_1122del NP_001341480.1:p.Asp373fs frameshift NM_001374461.1:c.2370_2373del NP_001361390.1:p.Asp790fs frameshift NM_130838.4:c.2370_2373del NP_570853.1:p.Asp790fs frameshift NR_148916.2:n.2938CAGA[1] non-coding transcript variant NC_000015.10:g.25340151CTGT[1] NC_000015.9:g.25585298CTGT[1] NG_009268.1:g.103825CAGA[1] LRG_15:g.103825CAGA[1] - Protein change
- D735fs, D751fs, D813fs, D393fs, D758fs, D790fs, D738fs, D810fs, D373fs
- Other names
- -
- Canonical SPDI
- NC_000015.10:25340149:TCTGTCTGT:TCTGT
-
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.
- -
- Links
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 |
40 | 1243 | |
| SNHG14 | - | - | GRCh38 | 4 | 1147 | |
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. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, single submitter
|
Nov 16, 2021 | RCV000144299.7 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
May 11, 2022 | RCV001092399.25 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(May 11, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002601535.2
First in ClinVar: Nov 19, 2022 Last updated: Mar 04, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation, as the last 63 amino acids are replaced with 6 different amino acids, and other loss-of-function variants … (more)
Frameshift variant predicted to result in protein truncation, as the last 63 amino acids are replaced with 6 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25212744, 35414530) (less)
|
|
|
Pathogenic
(Apr 01, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248894.27
First in ClinVar: May 12, 2020 Last updated: Dec 22, 2024 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Nov 16, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Angelman syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002240223.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Asp790Glufs*7) in the UBE3A gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Asp790Glufs*7) in the UBE3A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in UBE3A are known to be pathogenic (PMID: 25212744). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Angelman syndrome (PMID: 25212744). This variant is not present in population databases (gnomAD no frequency). (less)
|
|
|
Pathogenic
(Feb 14, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Angelman Syndrome
Affected status: yes
Allele origin:
germline
|
Baylor Genetics
Study: UBE3A Mutation Study
Accession: SCV000172050.1 First in ClinVar: Oct 04, 2014 Last updated: Oct 04, 2014
Comment:
Data collected from clinical UBE3A sequence analysis results
|
Number of individuals with the variant: 1
|
Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Asp790Glufs*7) in the UBE3A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in UBE3A are known to be pathogenic (PMID: 25212744). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Angelman syndrome (PMID: 25212744). This variant is not present in population databases (gnomAD no frequency).
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. |
Comment:
Frameshift variant predicted to result in protein truncation, as the last 63 amino acids are replaced with 6 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25212744, 35414530)
Comment:
This sequence change creates a premature translational stop signal (p.Asp790Glufs*7) in the UBE3A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in UBE3A are known to be pathogenic (PMID: 25212744). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with Angelman syndrome (PMID: 25212744). This variant is not present in population databases (gnomAD no frequency).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mutation Update for UBE3A variants in Angelman syndrome. | Sadikovic B | Human mutation | 2014 | PMID: 25212744 |
Text-mined citations for rs587781225 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Dec 22, 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.