ClinVar Genomic variation as it relates to human health
NM_130839.5(UBE3A):c.2567_2568del (p.Lys856fs)
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
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NM_130839.5(UBE3A):c.2567_2568del (p.Lys856fs)
Variation ID: 155984 Accession: VCV000155984.13
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 15q11.2 15: 25339188-25339189 (GRCh38) [ NCBI UCSC ] 15: 25584335-25584336 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Apr 15, 2024 Aug 11, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_130839.5:c.2567_2568del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_570854.1:p.Lys856fs frameshift NM_000462.5:c.2576_2577del NP_000453.2:p.Lys859fs frameshift NM_001354505.1:c.2567_2568del NP_001341434.1:p.Lys856fs frameshift NM_001354506.2:c.2507_2508del NP_001341435.1:p.Lys836fs frameshift NM_001354507.2:c.2507_2508del NP_001341436.1:p.Lys836fs frameshift NM_001354508.2:c.2507_2508del NP_001341437.1:p.Lys836fs frameshift NM_001354509.2:c.2507_2508del NP_001341438.1:p.Lys836fs frameshift NM_001354511.2:c.2507_2508del NP_001341440.1:p.Lys836fs frameshift NM_001354512.2:c.2507_2508del NP_001341441.1:p.Lys836fs frameshift NM_001354513.2:c.2507_2508del NP_001341442.1:p.Lys836fs frameshift NM_001354523.2:c.2507_2508del NP_001341452.1:p.Lys836fs frameshift NM_001354526.1:c.2507_2508del NP_001341455.1:p.Lys836fs frameshift NM_001354538.2:c.2567_2568del NP_001341467.1:p.Lys856fs frameshift NM_001354539.2:c.2507_2508del NP_001341468.1:p.Lys836fs frameshift NM_001354540.2:c.2507_2508del NP_001341469.1:p.Lys836fs frameshift NM_001354541.2:c.2507_2508del NP_001341470.1:p.Lys836fs frameshift NM_001354542.2:c.2507_2508del NP_001341471.1:p.Lys836fs frameshift NM_001354543.2:c.2507_2508del NP_001341472.1:p.Lys836fs frameshift NM_001354544.2:c.2507_2508del NP_001341473.1:p.Lys836fs frameshift NM_001354545.2:c.2411_2412del NP_001341474.1:p.Lys804fs frameshift NM_001354546.2:c.2390_2391del NP_001341475.1:p.Lys797fs frameshift NM_001354547.2:c.2351_2352del NP_001341476.1:p.Lys784fs frameshift NM_001354548.2:c.2351_2352del NP_001341477.1:p.Lys784fs frameshift NM_001354549.2:c.2342_2343del NP_001341478.1:p.Lys781fs frameshift NM_001354550.2:c.1316_1317del NP_001341479.1:p.Lys439fs frameshift NM_001354551.2:c.1256_1257del NP_001341480.1:p.Lys419fs frameshift NM_001374461.1:c.2507_2508del NP_001361390.1:p.Lys836fs frameshift NM_130838.4:c.2507_2508del NP_570853.1:p.Lys836fs frameshift NR_148916.2:n.3079_3080del non-coding transcript variant NC_000015.10:g.25339189_25339190del NC_000015.9:g.25584336_25584337del NG_009268.1:g.104793_104794del LRG_15:g.104793_104794del LRG_15t1:c.2507_2508del - Protein change
- K439fs, K797fs, K784fs, K804fs, K836fs, K856fs, K419fs, K781fs, K859fs
- Other names
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- Canonical SPDI
- NC_000015.10:25339187:TTT:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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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
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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. |
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Aug 11, 2022 | RCV000144307.13 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Apr 7, 2020 | RCV001008094.2 |
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
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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. |
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Likely pathogenic
(Apr 07, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001167839.1
First in ClinVar: Mar 16, 2020 Last updated: Mar 16, 2020 |
Comment:
Identified in two individuals with clinical suspicion for Angelman syndrome in published literature (Sadikovic et al., 2014), but additional clinical information and familial segregation information … (more)
Identified in two individuals with clinical suspicion for Angelman syndrome in published literature (Sadikovic et al., 2014), but additional clinical information and familial segregation information was not provided; Reported previously in the heterozygous state in a patient with a Rett-like phenotype (Iwama et al., 2019); Frameshift variant predicted to result in protein extension, as the last 17 amino acids are replaced with 23 different amino acids; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25212744, 30842224) (less)
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Pathogenic
(Apr 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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Angelman syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000934203.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the UBE3A protein in which other variant(s) (p.Glu837Argfs*4) have … (more)
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the UBE3A protein in which other variant(s) (p.Glu837Argfs*4) have been determined to be pathogenic (PMID: 11748306, 20034088). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 155984). This premature translational stop signal has been observed in individual(s) with clinical features of Angelman syndrome (PMID: 25212744; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys836Argfs*24) in the UBE3A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 17 amino acid(s) of the UBE3A protein. (less)
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Pathogenic
(Aug 11, 2022)
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criteria provided, single submitter
Method: clinical testing
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Angelman syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002549865.2
First in ClinVar: Jul 23, 2022 Last updated: Apr 15, 2024 |
Comment:
Criteria applied: PVS1_STR,PS2,PS4,PM2_SUP,PP4
Clinical Features:
Severe global developmental delay (present) , Seizure (present) , Absent speech (present)
Sex: female
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Pathogenic
(Feb 14, 2014)
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no assertion criteria provided
Method: clinical testing
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Angelman Syndrome
Affected status: yes
Allele origin:
germline
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Baylor Genetics
Study: UBE3A Mutation Study
Accession: SCV000172058.1 First in ClinVar: Oct 04, 2014 Last updated: Oct 04, 2014
Comment:
Data collected from clinical UBE3A sequence analysis results
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Number of individuals with the variant: 2
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Pathogenic
(Jun 07, 2020)
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no assertion criteria provided
Method: clinical testing
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Angelman syndrome
Affected status: yes
Allele origin:
germline
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Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001469260.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
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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 |
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Mutation Update for UBE3A variants in Angelman syndrome. | Sadikovic B | Human mutation | 2014 | PMID: 25212744 |
A novel UBE3A truncating mutation in large Tunisian Angelman syndrome pedigree. | Abaied L | American journal of medical genetics. Part A | 2010 | PMID: 20034088 |
Distinct phenotypes distinguish the molecular classes of Angelman syndrome. | Lossie AC | Journal of medical genetics | 2001 | PMID: 11748306 |
Text-mined citations for rs587781231 ...
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.