ClinVar Genomic variation as it relates to human health
NM_000135.4(FANCA):c.2606A>C (p.Gln869Pro)
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_000135.4(FANCA):c.2606A>C (p.Gln869Pro)
Variation ID: 215981 Accession: VCV000215981.42
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16q24.3 16: 89765062 (GRCh38) [ NCBI UCSC ] 16: 89831470 (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 26, 2018 May 12, 2024 Nov 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000135.4:c.2606A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000126.2:p.Gln869Pro missense NM_001286167.3:c.2606A>C NP_001273096.1:p.Gln869Pro missense NC_000016.10:g.89765062T>G NC_000016.9:g.89831470T>G NG_011706.1:g.56596A>C LRG_495:g.56596A>C LRG_495t1:c.2606A>C O15360:p.Gln869Pro - Protein change
- Q869P
- Other names
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- Canonical SPDI
- NC_000016.10:89765061:T:G
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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
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
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 | ||
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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
Help
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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FANCA | - | - |
GRCh38 GRCh37 |
4075 | 5199 | |
LOC130059837 | - | - | - | GRCh38 | - | 135 |
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. |
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Pathogenic (1) |
criteria provided, single submitter
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Nov 1, 2023 | RCV000199923.8 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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May 2, 2023 | RCV000674142.14 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Sep 15, 2021 | RCV001091062.18 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Aug 31, 2020 | RCV002252053.3 |
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. |
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Pathogenic
(Nov 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000253675.8
First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 869 of the FANCA protein (p.Gln869Pro). … (more)
This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 869 of the FANCA protein (p.Gln869Pro). This variant is present in population databases (rs780825099, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of Fanconi anemia (PMID: 15643609, 17924555, 29098742; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 215981). 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 expected to disrupt FANCA protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects FANCA function (PMID: 16720839, 17924555). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Sep 15, 2021)
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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: SCV001905620.1
First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
Clinical Features:
Renal dysplasia (present) , Bird-like facies (present) , Microphthalmia (present) , Thrombocytopenia (present) , Short nose (present) , Multiple renal cysts (present)
Sex: female
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Likely pathogenic
(Aug 31, 2020)
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criteria provided, single submitter
Method: clinical testing
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See cases
Affected status: yes
Allele origin:
germline
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Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV002523780.1
First in ClinVar: Jun 09, 2022 Last updated: Jun 09, 2022 |
Comment:
ACMG classification criteria: PS4, PM2, PM3, PP3
Clinical Features:
Vasculitis (present) , Muscle weakness (present) , Lactic acidosis (present) , Gastrointestinal inflammation (present) , Dyspnea (present) , Decreased circulating antibody level (present) , Chest … (more)
Vasculitis (present) , Muscle weakness (present) , Lactic acidosis (present) , Gastrointestinal inflammation (present) , Dyspnea (present) , Decreased circulating antibody level (present) , Chest pain (present) , Abnormal inflammatory response (present) , Abnormal autonomic nervous system physiology (present) , Abdominal pain (present) (less)
Geographic origin: Brazil
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Likely pathogenic
(Nov 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group A
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV002060197.2
First in ClinVar: Jan 15, 2022 Last updated: Nov 29, 2022 |
Comment:
NM_000135.2(FANCA):c.2606A>C(Q869P) is a missense variant classified as likely pathogenic in the context of Fanconi anemia complementation group A. Q869P has been observed in cases with … (more)
NM_000135.2(FANCA):c.2606A>C(Q869P) is a missense variant classified as likely pathogenic in the context of Fanconi anemia complementation group A. Q869P has been observed in cases with relevant disease (PMID: 29098742, 17924555, Czechowicz_2019_(no PMID; abstract), Shah_2019_(no PMID; abstract)). Functional assessments of this variant are available in the literature (PMID: 17924555, 16720839). Q869P has been observed in population frequency databases (gnomAD: NFE 0.003%). In summary, NM_000135.2(FANCA):c.2606A>C(Q869P) is a missense variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less)
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Likely pathogenic
(Jul 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group A
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000894102.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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Pathogenic
(May 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group A
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004196119.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(May 14, 2019)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group A
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002024575.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 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: SCV001246906.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Feb 28, 2020)
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no assertion criteria provided
Method: curation
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Fanconi anemia complementation group A
Affected status: yes
Allele origin:
germline
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Leiden Open Variation Database
Accession: SCV001425966.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
Comment:
Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Johan de Winter.
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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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A comprehensive approach to identification of pathogenic FANCA variants in Fanconi anemia patients and their families. | Kimble DC | Human mutation | 2018 | PMID: 29098742 |
Genetic subtyping of Fanconi anemia by comprehensive mutation screening. | Ameziane N | Human mutation | 2008 | PMID: 17924555 |
Evidence for subcomplexes in the Fanconi anemia pathway. | Medhurst AL | Blood | 2006 | PMID: 16720839 |
Spectrum of sequence variations in the FANCA gene: an International Fanconi Anemia Registry (IFAR) study. | Levran O | Human mutation | 2005 | PMID: 15643609 |
Text-mined citations for rs780825099 ...
HelpRecord last updated May 12, 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.