ClinVar Genomic variation as it relates to human health
NM_001625.4(AK2):c.84dup (p.Gly29fs)
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_001625.4(AK2):c.84dup (p.Gly29fs)
Variation ID: 1453536 Accession: VCV001453536.8
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 1p35.1 1: 33036744-33036745 (GRCh38) [ NCBI UCSC ] 1: 33502345-33502346 (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 28, 2022 Feb 20, 2024 Jan 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001625.4:c.84dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001616.1:p.Gly29fs frameshift NM_001199199.3:c.84dup NP_001186128.1:p.Gly29fs frameshift NM_001319139.3:c.-179dup 5 prime UTR NM_001319140.2:c.-179dup 5 prime UTR NM_001319141.3:c.84dup NP_001306070.1:p.Gly29fs frameshift NM_001319142.3:c.84dup NP_001306071.1:p.Gly29fs frameshift NM_001319143.2:c.84dup NP_001306072.1:p.Gly29fs frameshift NM_013411.5:c.84dup NP_037543.1:p.Gly29fs frameshift NR_134976.3:n.139dup non-coding transcript variant NC_000001.11:g.33036747dup NC_000001.10:g.33502348dup NG_016269.1:g.5147dup LRG_133:g.5147dup - Protein change
- G29fs
- Other names
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- Canonical SPDI
- NC_000001.11:33036744:TTT:TTTT
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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
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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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AK2 | - | - |
GRCh38 GRCh37 |
175 | 211 | |
LOC129930068 | - | - | - | GRCh38 | - | 26 |
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
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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 (2) |
criteria provided, multiple submitters, no conflicts
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Jan 18, 2023 | RCV002002459.7 |
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
(Feb 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Reticular dysgenesis
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002557751.1
First in ClinVar: Aug 08, 2022 Last updated: Aug 08, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with reticular dysgenesis (MIM#267500). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Hoenig et al. reported that around half of their cohort presented with additional haematological abnormalities. In addition, a recurrent missense variant resulted in a variable phenotype in 3 independent families (PMID: 28331055). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v3) <0.01 for a recessive condition (1 heterozygote, 0 homozygotes). (SP) 0702 - Other NMD-predicted variants comparable to the one identified in this case have strong previous evidence for pathogenicity. Variants predicted to result in NMD have been reported in multiple patients with reticular dysgenesis (PMID: 19043416, 19043417, 28331055, 30778343). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Pathogenic
(Jan 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Reticular dysgenesis
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002228736.4
First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1453536). This variant has not been … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1453536). This variant has not been reported in the literature in individuals affected with AK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly29Argfs*9) in the AK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AK2 are known to be pathogenic (PMID: 19043416, 19043417, 19414857). (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, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India. | Aluri J | Frontiers in immunology | 2019 | PMID: 30778343 |
Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome. | Hoenig M | Blood | 2017 | PMID: 28331055 |
Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome. | Poliani PL | Blood | 2009 | PMID: 19414857 |
Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2. | Pannicke U | Nature genetics | 2009 | PMID: 19043417 |
Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness. | Lagresle-Peyrou C | Nature genetics | 2009 | PMID: 19043416 |
Text-mined citations for rs1640610158 ...
HelpRecord last updated Feb 28, 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.