rs1555729503
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005499.3(UBA2):c.816_817del(p.Trp273AlafsTer13) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
UBA2
NM_005499.3 frameshift
NM_005499.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.37
Genes affected
UBA2 (HGNC:30661): (ubiquitin like modifier activating enzyme 2) Posttranslational modification of proteins by the addition of the small protein SUMO (see SUMO1; MIM 601912), or sumoylation, regulates protein structure and intracellular localization. SAE1 (MIM 613294) and UBA2 form a heterodimer that functions as a SUMO-activating enzyme for the sumoylation of proteins (Okuma et al., 1999 [PubMed 9920803]).[supplied by OMIM, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-34450307-CTA-C is Pathogenic according to our data. Variant chr19-34450307-CTA-C is described in ClinVar as [Pathogenic]. Clinvar id is 521193.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBA2 | NM_005499.3 | c.816_817del | p.Trp273AlafsTer13 | frameshift_variant | 9/17 | ENST00000246548.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBA2 | ENST00000246548.9 | c.816_817del | p.Trp273AlafsTer13 | frameshift_variant | 9/17 | 1 | NM_005499.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | May 06, 2023 | The c.816_817delAT (p.W273Afs*13) alteration, located in exon 9 (coding exon 9) of the UBA2 gene, consists of a deletion of 2 nucleotides from position 816 to 817, causing a translational frameshift with a predicted alternate stop codon after 13 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported to segregate with disease in a family with features of ACCES syndrome (Schnur, 2021). Based on the available evidence, this alteration is classified as pathogenic. - |
ACCES syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 14, 2022 | - - |
Computational scores
Source:
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Calibrated prediction
Score
Prediction
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at