ClinVar Genomic variation as it relates to human health
NM_015338.6(ASXL1):c.2077C>T (p.Arg693Ter)
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_015338.6(ASXL1):c.2077C>T (p.Arg693Ter)
Variation ID: 620281 Accession: VCV000620281.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20q11.21 20: 32434789 (GRCh38) [ NCBI UCSC ] 20: 31022592 (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 Mar 19, 2019 Jun 29, 2024 Mar 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_015338.6:c.2077C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_056153.2:p.Arg693Ter nonsense NM_001363734.1:c.1894C>T NP_001350663.1:p.Arg632Ter nonsense NC_000020.11:g.32434789C>T NC_000020.10:g.31022592C>T NG_027868.1:g.81446C>T LRG_630:g.81446C>T LRG_630t1:c.2077C>T LRG_630p1:p.Arg693Ter - Protein change
- R693*, R632*
- Other names
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- Canonical SPDI
- NC_000020.11:32434788:C: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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
The Genome Aggregation Database (gnomAD) 0.00002
Exome Aggregation Consortium (ExAC) 0.00005
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- Links
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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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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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ASXL1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
994 | 1016 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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 (1) |
criteria provided, single submitter
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Aug 10, 2018 | RCV000760645.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 25, 2024 | RCV002282359.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 14, 2022 | RCV003147544.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 25, 2024 | RCV004526768.1 |
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
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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
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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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Pathogenic
(Aug 10, 2018)
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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: SCV000890537.1
First in ClinVar: Mar 19, 2019 Last updated: Mar 19, 2019 |
Comment:
The R693X variant in the ASXL1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This … (more)
The R693X variant in the ASXL1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function through protein truncation. The R693X variant is observed in 1/30934 (0.003%) alleles in large population cohorts. We interpret R693X as a pathogenic variant. (less)
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Pathogenic
(Jan 14, 2022)
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criteria provided, single submitter
Method: clinical testing
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Myelodysplastic syndrome
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV003836203.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(Mar 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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Deficiency of iodide peroxidase
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005039011.1
First in ClinVar: May 07, 2024 Last updated: May 07, 2024 |
Comment:
Variant summary: TPO c.2077C>T (p.Arg693Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: TPO c.2077C>T (p.Arg693Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251222 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2077C>T has been reported in the literature in individuals affected with Deficiency Of Iodide Peroxidase. These report(s) do not provide unequivocal conclusions about association of the variant with Deficiency Of Iodide Peroxidase. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Pathogenic
(Mar 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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Bohring-Opitz syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002572182.3
First in ClinVar: Sep 17, 2022 Last updated: Jun 29, 2024 |
Comment:
Variant summary: ASXL1 c.2077C>T (p.Arg693X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: ASXL1 c.2077C>T (p.Arg693X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this variant have been classified as pathogenic and reported in HGMD in association with Bohring-Opitz syndrome. The variant allele was found at a frequency of 4e-06 in 251152 control chromosomes. To our knowledge, no occurrence of c.2077C>T in individuals affected with Bohring-Opitz Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 620281). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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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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Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. | Döhner H | Blood | 2017 | PMID: 27895058 |
Genomic Classification and Prognosis in Acute Myeloid Leukemia. | Papaemmanuil E | The New England journal of medicine | 2016 | PMID: 27276561 |
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. | Arber DA | Blood | 2016 | PMID: 27069254 |
Integrated genomic profiling, therapy response, and survival in adult acute myelogenous leukemia. | Parkin B | Clinical cancer research : an official journal of the American Association for Cancer Research | 2015 | PMID: 25652455 |
ASXL1 mutations in younger adult patients with acute myeloid leukemia: a study by the German-Austrian Acute Myeloid Leukemia Study Group. | Paschka P | Haematologica | 2015 | PMID: 25596267 |
ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients. | Patnaik MM | Leukemia | 2014 | PMID: 24695057 |
CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: an international study of 570 patients. | Tefferi A | Leukemia | 2014 | PMID: 24496303 |
Impact of mutational status on outcomes in myelofibrosis patients treated with ruxolitinib in the COMFORT-II study. | Guglielmelli P | Blood | 2014 | PMID: 24458439 |
Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome. | Chen TC | Blood cancer journal | 2014 | PMID: 24442206 |
Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice. | Wang J | Blood | 2014 | PMID: 24255920 |
Prognostic score including gene mutations in chronic myelomonocytic leukemia. | Itzykson R | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2013 | PMID: 23690417 |
Mutations and prognosis in primary myelofibrosis. | Vannucchi AM | Leukemia | 2013 | PMID: 23619563 |
ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome. | Schnittger S | Leukemia | 2013 | PMID: 23018865 |
Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms. | Brecqueville M | Genes, chromosomes & cancer | 2012 | PMID: 22489043 |
Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value. | Pratcorona M | Haematologica | 2012 | PMID: 22058207 |
ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category. | Metzeler KH | Blood | 2011 | PMID: 22031865 |
Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. | Shen Y | Blood | 2011 | PMID: 21881046 |
Prognostic significance of ASXL1 mutations in patients with myelodysplastic syndromes. | Thol F | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2011 | PMID: 21576631 |
ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia. | Gelsi-Boyer V | British journal of haematology | 2010 | PMID: 20880116 |
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Text-mined citations for rs373221034 ...
HelpRecord last updated Jul 07, 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.