ClinVar Genomic variation as it relates to human health
NM_003721.4(RFXANK):c.634C>T (p.Arg212Ter)
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_003721.4(RFXANK):c.634C>T (p.Arg212Ter)
Variation ID: 1074711 Accession: VCV001074711.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.11 19: 19199156 (GRCh38) [ NCBI UCSC ] 19: 19309965 (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 May 10, 2021 Feb 14, 2024 Oct 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003721.4:c.634C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003712.1:p.Arg212Ter nonsense NM_001278727.2:c.568C>T NP_001265656.1:p.Arg190Ter nonsense NM_001278728.2:c.565C>T NP_001265657.1:p.Arg189Ter nonsense NM_001370233.1:c.634C>T NP_001357162.1:p.Arg212Ter nonsense NM_001370234.1:c.568C>T NP_001357163.1:p.Arg190Ter nonsense NM_001370235.1:c.631C>T NP_001357164.1:p.Arg211Ter nonsense NM_001370236.1:c.631C>T NP_001357165.1:p.Arg211Ter nonsense NM_001370237.1:c.631C>T NP_001357166.1:p.Arg211Ter nonsense NM_001370238.1:c.634C>T NP_001357167.1:p.Arg212Ter nonsense NM_134440.3:c.565C>T NP_604389.1:p.Arg189Ter nonsense NC_000019.10:g.19199156C>T NC_000019.9:g.19309965C>T NG_007432.1:g.11958C>T LRG_102:g.11958C>T - Protein change
- R189*, R190*, R211*, R212*
- Other names
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- Canonical SPDI
- NC_000019.10:19199155: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.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
- 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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RFXANK | - | - |
GRCh38 GRCh37 |
239 | 276 |
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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Oct 13, 2023 | RCV001388116.9 |
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 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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MHC class II deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
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Randwick Genomics Laboratory, Prince of Wales Hospital Sydney, Australia, New South Wales Health Pathology
Accession: SCV001763560.1
First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021 |
Comment:
A substitution in codon 212 in the penultimate exon likely to be subject to nonsense mediated mRNA decay. This variant has been published previously as … (more)
A substitution in codon 212 in the penultimate exon likely to be subject to nonsense mediated mRNA decay. This variant has been published previously as a pathogenic variant (PMID:12618906). This variant has been classified as pathogenic according to ACMG criteria with PVS1, PM2 and PP5. (less)
Sex: male
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Pathogenic
(Oct 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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MHC class II deficiency
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002600468.1
First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022 |
Comment:
Variant summary: RFXANK c.634C>T (p.Arg212X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: RFXANK c.634C>T (p.Arg212X) 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. The variant allele was found at a frequency of 8e-06 in 250558 control chromosomes (gnomAD). c.634C>T has been reported in the literature as a biallelic genotype in multiple individuals affected with MHC class II deficiency (e.g. Wiszniewski_2003, Abolhassani_2018, Suratannon_2020, Cakir_2021). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Wiszniewski_2003). The most pronounced variant effect resulted in a severe reduction of RFXANK transcripts and complete loss of protein expression in cells from a homozygous individual. Two submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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MHC class II deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001588977.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg212*) in the RFXANK gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg212*) in the RFXANK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RFXANK are known to be pathogenic (PMID: 10803838, 16166641, 21908431). This variant is present in population databases (rs747402973, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with clinical features of MHC class II deficiency (PMID: 12618906). ClinVar contains an entry for this variant (Variation ID: 1074711). For these reasons, this variant has been 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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Early onset congenital diarrheas; single center experience. | Cakir M | Pediatrics and neonatology | 2021 | PMID: 34330684 |
Rapid Low-Cost Microarray-Based Genotyping for Genetic Screening in Primary Immunodeficiency. | Suratannon N | Frontiers in immunology | 2020 | PMID: 32373116 |
Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency. | Abolhassani H | The Journal of allergy and clinical immunology | 2018 | PMID: 28916186 |
Major histocompatibility complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients. | Ouederni M | Blood | 2011 | PMID: 21908431 |
New functions of the major histocompatibility complex class II-specific transcription factor RFXANK revealed by a high-resolution mutagenesis study. | Krawczyk M | Molecular and cellular biology | 2005 | PMID: 16166641 |
Novel mutations in the RFXANK gene: RFX complex containing in-vitro-generated RFXANK mutant binds the promoter without transactivating MHC II. | Wiszniewski W | Immunogenetics | 2003 | PMID: 12618906 |
Founder effect for a 26-bp deletion in the RFXANK gene in North African major histocompatibility complex class II-deficient patients belonging to complementation group B. | Wiszniewski W | Immunogenetics | 2000 | PMID: 10803838 |
Text-mined citations for rs747402973 ...
HelpRecord last updated Feb 20, 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.