ClinVar Genomic variation as it relates to human health
NM_006118.4(HAX1):c.130_131insA (p.Trp44Ter)
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_006118.4(HAX1):c.130_131insA (p.Trp44Ter)
Variation ID: 4651 Accession: VCV000004651.33
- Type and length
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Insertion, 1 bp
- Location
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Cytogenetic: 1q21.3 1: 154273412-154273413 (GRCh38) [ NCBI UCSC ] 1: 154245888-154245889 (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 Apr 4, 2013 Oct 8, 2024 Sep 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_006118.4:c.130_131insA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006109.2:p.Trp44Ter nonsense NM_001018837.2:c.54-68_54-67insA intron variant NC_000001.11:g.154273412_154273413insA NC_000001.10:g.154245888_154245889insA NG_007369.1:g.5850_5851insA LRG_64:g.5850_5851insA LRG_64t1:c.130_131insA LRG_64p1:p.Trp44Ter - Protein change
- W44*
- Other names
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- Canonical SPDI
- NC_000001.11:154273412::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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- Comment on variant
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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HAX1 | - | - |
GRCh38 GRCh37 |
386 | 409 |
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 (4) |
criteria provided, multiple submitters, no conflicts
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Jun 3, 2022 | RCV000004914.7 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Sep 18, 2023 | RCV001090409.26 |
Submissions - Germline
Classification
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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
Help
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
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447670.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Neutropenia (present)
Sex: male
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Pathogenic
(May 12, 2016)
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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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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449851.1
First in ClinVar: Dec 10, 2020 Last updated: Dec 10, 2020 |
Number of individuals with the variant: 10
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Pathogenic
(Dec 28, 2021)
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criteria provided, single submitter
Method: clinical testing
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Kostmann syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
unknown
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Genomics Facility, Ludwig-Maximilians-Universität München
Accession: SCV002073899.1
First in ClinVar: Feb 09, 2022 Last updated: Feb 09, 2022 |
Clinical Features:
Neutropenia (present)
Sex: female
Tissue: PBMCs
Method: Agilent V6+UTR exome enrichment, Illumina NextSeq 500 sequencing
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Pathogenic
(Jun 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Kostmann syndrome
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn
Accession: SCV002757842.1
First in ClinVar: Dec 03, 2022 Last updated: Dec 03, 2022 |
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Pathogenic
(Sep 18, 2023)
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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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Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005197085.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Pathogenic
(May 01, 2019)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001245950.25
First in ClinVar: May 12, 2020 Last updated: Oct 08, 2024 |
Number of individuals with the variant: 2
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Pathogenic
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Kostmann syndrome
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002058599.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are … (more)
Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000004651, PMID:17187068). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Failure to thrive (present) , Hepatosplenomegaly (present) , Neutropenia (present) , Recurrent lower respiratory tract infections (present) , Recurrent infections (present)
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Pathogenic
(May 15, 2008)
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no assertion criteria provided
Method: literature only
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NEUTROPENIA, SEVERE CONGENITAL, 3, AUTOSOMAL RECESSIVE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000025090.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In affected members of 3 unrelated Kurdish families with Kostmann disease (SCN3; 610738), Klein et al. (2007) detected homozygosity for a 1-bp insertion (130insA) in … (more)
In affected members of 3 unrelated Kurdish families with Kostmann disease (SCN3; 610738), Klein et al. (2007) detected homozygosity for a 1-bp insertion (130insA) in exon 2 of the HAX1 gene that led to introduction of a premature stop codon at trp44 (W44X). Healthy sibs and parents had at least 1 allele with the wildtype sequence. HAX1 was absent in cells from affected individuals, as shown by protein blot analysis. Sequencing of the HAX1 gene in 63 additional individuals found 15 with the same insertion as the index families. The W44X mutation exclusively affects the full-length transcript (Germeshausen et al., 2008). (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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The Utility of Next-Generation Sequencing for Primary Immunodeficiency Disorders: Experience from a Clinical Diagnostic Laboratory. | Bisgin A | BioMed research international | 2018 | PMID: 29888287 |
Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations. | Germeshausen M | Blood | 2008 | PMID: 18337561 |
HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). | Klein C | Nature genetics | 2007 | PMID: 17187068 |
Text-mined citations for rs1572018284 ...
HelpRecord last updated Oct 08, 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.
ClinGen staff contributed the HGVS expression for this variant.