ClinVar Genomic variation as it relates to human health
NM_000037.4(ANK1):c.2803C>T (p.Arg935Ter)
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_000037.4(ANK1):c.2803C>T (p.Arg935Ter)
Variation ID: 1330761 Accession: VCV001330761.39
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8p11.21 8: 41696520 (GRCh38) [ NCBI UCSC ] 8: 41554038 (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 Jan 8, 2022 Feb 20, 2024 Jan 24, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000037.4:c.2803C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000028.3:p.Arg935Ter nonsense NM_000037.3:c.2803C>T NM_001142446.2:c.2926C>T NP_001135918.1:p.Arg976Ter nonsense NM_020475.3:c.2803C>T NP_065208.2:p.Arg935Ter nonsense NM_020476.3:c.2803C>T NP_065209.2:p.Arg935Ter nonsense NM_020477.3:c.2803C>T NP_065210.2:p.Arg935Ter nonsense NC_000008.11:g.41696520G>A NC_000008.10:g.41554038G>A NG_012820.2:g.205243C>T - Protein change
- R935*, R976*
- Other names
- p.Arg935*
- Canonical SPDI
- NC_000008.11:41696519:G:A
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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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- 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 | ||
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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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ANK1 | - | - |
GRCh38 GRCh37 |
958 | 1115 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Apr 25, 2023 | RCV001802420.13 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 24, 2024 | RCV001869471.5 |
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
(Mar 01, 2022)
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criteria provided, single submitter
Method: research
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Hereditary spherocytosis type 1
Affected status: yes
Allele origin:
de novo
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Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University
Accession: SCV002499992.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
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Pathogenic
(Dec 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004227601.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
PP5_very_strong, PM2, PM6, PS4_moderate, PVS1
Number of individuals with the variant: 1
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Pathogenic
(Apr 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spherocytosis type 1
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003817329.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 24, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002247483.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg935*) in the ANK1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg935*) in the ANK1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANK1 are known to be pathogenic (PMID: 8640229). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary spherocytosis (PMID: 27427187, 29597199, 31122244, 32436265, 33074480, 33620149). This variant is also known as p.Arg976*. ClinVar contains an entry for this variant (Variation ID: 1330761). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 29, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spherocytosis type 1
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002048031.4
First in ClinVar: Jan 08, 2022 Last updated: Feb 20, 2024 |
Comment:
The ANK1 c.2803C>T; p.Arg935Ter variant is reported in the literature in multiple individuals with spherocytosis or hemolytic anemia (Choi 2019, Del Orbe Barreto 2016, Gao … (more)
The ANK1 c.2803C>T; p.Arg935Ter variant is reported in the literature in multiple individuals with spherocytosis or hemolytic anemia (Choi 2019, Del Orbe Barreto 2016, Gao 2018, Muramatsu 2017, Tole 2020, Wang 2018). This variant is also reported in ClinVar (Variation ID: 1330761). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Choi HS et al. Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte. Orphanet J Rare Dis. 2019 May 23. PMID: 31122244 Del Orbe Barreto R et al. Detection of new pathogenic mutations in patients with congenital haemolytic anaemia using next-generation sequencing. Int J Lab Hematol. 2016 Dec. PMID: 27427187 Gao Y et al. Diagnosis of Hereditary Spherocytosis and Secondary Hemochromatosis in a Patient with Jaundice. Acta Haematol. 2018 PMID: 29597199 Muramatsu H et al. Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. Genet Med. 2017 Jul. PMID: 28102861 Tole S et al. Genotype-phenotype correlation in children with hereditary spherocytosis. Br J Haematol. 2020 Nov. PMID: 32436265 Wang R et al. Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci China Life Sci. 2018 Aug. PMID: 29572776 (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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Clinical and Genetic Etiologies of Neonatal Unconjugated Hyperbilirubinemia in the China Neonatal Genomes Project. | Mei H | The Journal of pediatrics | 2022 | PMID: 34953813 |
Clinical manifestation and phenotypic analysis of novel gene mutation in 28 Chinese children with hereditary spherocytosis. | Xie F | Molecular genetics & genomic medicine | 2021 | PMID: 33620149 |
Characterization of hereditary red blood cell membranopathies using combined targeted next-generation sequencing and osmotic gradient ektacytometry. | Vives-Corrons JL | International journal of hematology | 2021 | PMID: 33074480 |
Red cell membrane disorders: structure meets function. | Risinger M | Blood | 2020 | PMID: 32702754 |
Genotype-phenotype correlation in children with hereditary spherocytosis. | Tole S | British journal of haematology | 2020 | PMID: 32436265 |
Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte. | Choi HS | Orphanet journal of rare diseases | 2019 | PMID: 31122244 |
Diagnosis of Hereditary Spherocytosis and Secondary Hemochromatosis in a Patient with Jaundice. | Gao Y | Acta haematologica | 2018 | PMID: 29597199 |
Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. | Muramatsu H | Genetics in medicine : official journal of the American College of Medical Genetics | 2017 | PMID: 28102861 |
Detection of new pathogenic mutations in patients with congenital haemolytic anaemia using next-generation sequencing. | Del Orbe Barreto R | International journal of laboratory hematology | 2016 | PMID: 27427187 |
Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis. | Eber SW | Nature genetics | 1996 | PMID: 8640229 |
Text-mined citations for rs2150597061 ...
HelpRecord last updated Mar 17, 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.