VCV000573103.11 - ClinVar

NM_172245.4(CSF2RA):c.191A>G (p.Asp64Gly)

Germline

Classification

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.

(5)

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.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_172245.4(CSF2RA):c.191A>G (p.Asp64Gly)

Variation ID: 573103 Accession: VCV000573103.11

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Yp11.2 Xp22.33 X: 1285892 (GRCh38) [ NCBI UCSC ] Y: 1285892 (GRCh38) [ NCBI UCSC ] X: 1404785 (GRCh37) [ NCBI UCSC ] Y: 1354785 (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	Oct 10, 2018	Oct 8, 2024	Oct 17, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_172245.4:c.191A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_758448.1:p.Asp64Gly	missense
NM_001161529.2:c.191A>G	NP_001155001.1:p.Asp64Gly	missense
NM_001161530.2:c.191A>G	NP_001155002.1:p.Asp64Gly	missense
NM_001161531.2:c.191A>G	NP_001155003.1:p.Asp64Gly	missense
NM_001161532.2:c.-180-2627A>G		intron variant
NM_001379153.1:c.191A>G	NP_001366082.1:p.Asp64Gly	missense
NM_001379154.1:c.191A>G	NP_001366083.1:p.Asp64Gly	missense
NM_001379155.1:c.191A>G	NP_001366084.1:p.Asp64Gly	missense
NM_001379156.1:c.191A>G	NP_001366085.1:p.Asp64Gly	missense
NM_001379158.1:c.191A>G	NP_001366087.1:p.Asp64Gly	missense
NM_001379159.1:c.191A>G	NP_001366088.1:p.Asp64Gly	missense
NM_001379160.1:c.191A>G	NP_001366089.1:p.Asp64Gly	missense
NM_001379161.1:c.191A>G	NP_001366090.1:p.Asp64Gly	missense
NM_001379162.1:c.191A>G	NP_001366091.1:p.Asp64Gly	missense
NM_001379163.1:c.191A>G	NP_001366092.1:p.Asp64Gly	missense
NM_001379164.1:c.191A>G	NP_001366093.1:p.Asp64Gly	missense
NM_001379165.1:c.191A>G	NP_001366094.1:p.Asp64Gly	missense
NM_001379166.1:c.191A>G	NP_001366095.1:p.Asp64Gly	missense
NM_001379167.1:c.191A>G	NP_001366096.1:p.Asp64Gly	missense
NM_001379168.1:c.191A>G	NP_001366097.1:p.Asp64Gly	missense
NM_001379169.1:c.191A>G	NP_001366098.1:p.Asp64Gly	missense
NM_006140.6:c.191A>G	NP_006131.2:p.Asp64Gly	missense
NM_172246.4:c.191A>G	NP_758449.1:p.Asp64Gly	missense
NM_172247.3:c.191A>G	NP_758450.1:p.Asp64Gly	missense
NM_172249.4:c.191A>G	NP_758452.1:p.Asp64Gly	missense
NR_027760.3:n.371A>G		non-coding transcript variant
NC_000023.11:g.1285892A>G
NC_000024.10:g.1285892A>G
NC_000023.10:g.1404785A>G
NC_000024.9:g.1354785A>G
NG_012280.1:g.22093A>G
LRG_186:g.22093A>G

... more HGVS ... less HGVS

Protein change

D64G

Other names

Canonical SPDI

NC_000024.10:1285891:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.00026 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.00026

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00038

1000 Genomes Project 30x 0.00021

Exome Aggregation Consortium (ExAC) 0.00050

The Genome Aggregation Database (gnomAD), exomes 0.00055

The Genome Aggregation Database (gnomAD) 0.00059

Trans-Omics for Precision Medicine (TOPMed) 0.00059

Links

dbSNP: rs150743648 VarSome

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
Gene	OMIM	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.
Surfactant metabolism dysfunction, pulmonary, 4	Uncertain significance (3)	criteria provided, multiple submitters, no conflicts	Oct 17, 2022	RCV000694681.9
not provided	Uncertain significance (1)	criteria provided, single submitter	Mar 30, 2021	RCV003227831.1
CSF2RA-related disorder	Likely benign (1)	no assertion criteria provided	Jan 15, 2024	RCV003892550.2

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.
Uncertain significance (Oct 07, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Surfactant metabolism dysfunction, pulmonary, 4 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002778008.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain significance (Oct 17, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Surfactant metabolism dysfunction, pulmonary, 4 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000823138.6 First in ClinVar: Oct 10, 2018 Last updated: Feb 07, 2023	Publications: PubMed (1) PubMed: 28492532 Comment: This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 64 of the CSF2RA protein … (more) This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 64 of the CSF2RA protein (p.Asp64Gly). This variant is present in population databases (no rsID available, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CSF2RA-related conditions. ClinVar contains an entry for this variant (Variation ID: 573103). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CSF2RA protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Mar 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago Accession: SCV003924174.1 First in ClinVar: May 20, 2023 Last updated: May 20, 2023	Comment: CSF2RA NM_001161531.1 exon 4 p.Asp64Gly (c.191A>G): This variant has not been reported in the literature but is present in 0.06% (79/126408) of European alleles in … (more) CSF2RA NM_001161531.1 exon 4 p.Asp64Gly (c.191A>G): This variant has not been reported in the literature but is present in 0.06% (79/126408) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/X-1404785-A-G). This variant is present in ClinVar (Variation ID:575469). Evolutionary conservation for this variant is limited or unavailable; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (less)
Likely benign (Jan 15, 2024)	no assertion criteria provided Method: clinical testing	CSF2RA-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004713937.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
not provided (-)	no classification provided Method: phenotyping only	Surfactant metabolism dysfunction, pulmonary, 4 Affected status: unknown Allele origin: unknown	GenomeConnect - Invitae Patient Insights Network Accession: SCV001749498.1 First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021	Comment: Variant interpreted as Uncertain significance and reported on 12-04-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided … (more) Variant interpreted as Uncertain significance and reported on 12-04-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less) Clinical Features: Hypermetropia (present) , Abnormal lens morphology (present) , Asthma (present) , Bleeding with minor or no trauma (present) , Bruising susceptibility (present) , Epistaxis (present) … (more) Hypermetropia (present) , Abnormal lens morphology (present) , Asthma (present) , Bleeding with minor or no trauma (present) , Bruising susceptibility (present) , Epistaxis (present) , Persistent bleeding after trauma (present) , Autoimmunity (present) , Immunodeficiency (present) , Abnormal inflammatory response (present) , Recurrent infections (present) , Rheumatoid arthritis (present) , Feeding difficulties (present) , Abnormal intestine morphology (present) , Abnormal large intestine morphology (present) , Obesity (present) , Abnormal muscle physiology (present) , Increased susceptibility to fractures (present) , Abnormal renal physiology (present) , Anxiety (present) , Depression (present) , Premature birth (present) (less) Indication for testing: Diagnostic Age: 30-39 years Sex: female Testing laboratory: Invitae Date variant was reported to submitter: 2018-12-04 Testing laboratory interpretation: Uncertain significance

Comment:

This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 64 of the CSF2RA protein (p.Asp64Gly). This variant is present in population databases (no rsID available, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CSF2RA-related conditions. ClinVar contains an entry for this variant (Variation ID: 573103). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CSF2RA protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

CSF2RA NM_001161531.1 exon 4 p.Asp64Gly (c.191A>G): This variant has not been reported in the literature but is present in 0.06% (79/126408) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/X-1404785-A-G). This variant is present in ClinVar (Variation ID:575469). Evolutionary conservation for this variant is limited or unavailable; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

Comment:

Variant interpreted as Uncertain significance and reported on 12-04-2018 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs150743648 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 13, 2024

ClinVar Genomic variation as it relates to human health

NM_172245.4(CSF2RA):c.191A>G (p.Asp64Gly)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs150743648 ...