For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with CSF2RA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu117Valfs*16) in the CSF2RA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CSF2RA are known to be pathogenic (PMID: 20622029, 25425184).
ClinVar Genomic variation as it relates to human health
NM_172245.4(CSF2RA):c.350_353del (p.Glu117fs)
Germline
Classification
Help
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.
(1)
Help
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.
Pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_172245.4(CSF2RA):c.350_353del (p.Glu117fs)
Variation ID: 2088110 Accession: VCV002088110.2
- Type and length
-
Microsatellite, 4 bp
- Location
-
Cytogenetic: Yp11.2 Xp22.33 X: 1288761-1288764 (GRCh38) [ NCBI UCSC ] Y: 1288761-1288764 (GRCh38) [ NCBI UCSC ] X: 1407654-1407657 (GRCh37) [ NCBI UCSC ] Y: 1357654-1357657 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Feb 8, 2023 Feb 20, 2024 Jan 19, 2022 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_172245.4:c.350_353del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_758448.1:p.Glu117fs frameshift NM_001161529.2:c.350_353del NP_001155001.1:p.Glu117fs frameshift NM_001161530.2:c.350_353del NP_001155002.1:p.Glu117fs frameshift NM_001161531.2:c.350_353del NP_001155003.1:p.Glu117fs frameshift NM_001161532.2:c.-54AGGG[1] 5 prime UTR NM_001379153.1:c.350_353del NP_001366082.1:p.Glu117fs frameshift NM_001379154.1:c.350_353del NP_001366083.1:p.Glu117fs frameshift NM_001379155.1:c.350_353del NP_001366084.1:p.Glu117fs frameshift NM_001379156.1:c.350_353del NP_001366085.1:p.Glu117fs frameshift NM_001379157.1:c.346_349AGGG[1] NP_001366086.1:p.Glu117Valfs frameshift NM_001379158.1:c.350_353del NP_001366087.1:p.Glu117fs frameshift NM_001379159.1:c.350_353del NP_001366088.1:p.Glu117fs frameshift NM_001379160.1:c.350_353del NP_001366089.1:p.Glu117fs frameshift NM_001379161.1:c.350_353del NP_001366090.1:p.Glu117fs frameshift NM_001379162.1:c.350_353del NP_001366091.1:p.Glu117fs frameshift NM_001379163.1:c.350_353del NP_001366092.1:p.Glu117fs frameshift NM_001379164.1:c.350_353del NP_001366093.1:p.Glu117fs frameshift NM_001379165.1:c.350_353del NP_001366094.1:p.Glu117fs frameshift NM_001379166.1:c.350_353del NP_001366095.1:p.Glu117fs frameshift NM_001379167.1:c.350_353del NP_001366096.1:p.Glu117fs frameshift NM_001379168.1:c.350_353del NP_001366097.1:p.Glu117fs frameshift NM_001379169.1:c.350_353del NP_001366098.1:p.Glu117fs frameshift NM_006140.6:c.350_353del NP_006131.2:p.Glu117fs frameshift NM_172246.4:c.350_353del NP_758449.1:p.Glu117fs frameshift NM_172247.3:c.350_353del NP_758450.1:p.Glu117fs frameshift NM_172249.4:c.350_353del NP_758452.1:p.Glu117fs frameshift NR_027760.3:n.526AGGG[1] non-coding transcript variant NC_000023.11:g.1288761AGGG[1] NC_000024.10:g.1288761AGGG[1] NC_000023.10:g.1407654AGGG[1] NC_000024.9:g.1357654AGGG[1] NG_012280.1:g.24962AGGG[1] LRG_186:g.24962AGGG[1] LRG_186t1:c.346_349AGGG[1] LRG_186p1:p.Glu117Valfs LRG_186t2:c.346_349AGGG[1] LRG_186p2:p.Glu117Valfs LRG_186t3:c.346_349AGGG[1] LRG_186p3:p.Glu117Valfs - Protein change
- E117fs
- Other names
- -
- Canonical SPDI
- NC_000024.10:1288760:AGGGAGGG:AGGG
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- 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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
| CSF2RA |
|
- | - |
GRCh38 GRCh38 |
427 | 556 |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (1) |
criteria provided, single submitter
|
Jan 19, 2022 | RCV003009901.3 |
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
Help
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
Help
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jan 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Surfactant metabolism dysfunction, pulmonary, 4
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003302274.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this … (more)
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with CSF2RA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu117Valfs*16) in the CSF2RA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CSF2RA are known to be pathogenic (PMID: 20622029, 25425184). (less)
|
Comment:
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. |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with CSF2RA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu117Valfs*16) in the CSF2RA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CSF2RA are known to be pathogenic (PMID: 20622029, 25425184).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Characterization of CSF2RA mutation related juvenile pulmonary alveolar proteinosis. | Hildebrandt J | Orphanet journal of rare diseases | 2014 | PMID: 25425184 |
| Hereditary pulmonary alveolar proteinosis: pathogenesis, presentation, diagnosis, and therapy. | Suzuki T | American journal of respiratory and critical care medicine | 2010 | PMID: 20622029 |
Text-mined citations for this variant ...
HelpRecord last updated Sep 29, 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.