ClinVar Genomic variation as it relates to human health
NM_000135.4(FANCA):c.1115_1118del (p.Val372fs)
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.1115_1118del (p.Val372fs)
Variation ID: 3440 Accession: VCV000003440.51
- Type and length
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Microsatellite, 4 bp
- Location
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Cytogenetic: 16q24.3 16: 89792034-89792037 (GRCh38) [ NCBI UCSC ] 16: 89858442-89858445 (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 3, 2013 May 12, 2024 Apr 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000135.4:c.1115_1118del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000126.2:p.Val372fs frameshift NM_000135.4:c.1115_1118delTTGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000135.3:c.1115_1118del NM_001286167.3:c.1115_1118del NP_001273096.1:p.Val372fs frameshift NC_000016.10:g.89792035CAAC[1] NC_000016.9:g.89858443CAAC[1] NG_011706.1:g.29617TTGG[1] LRG_495:g.29617TTGG[1] LRG_495t1:c.1115_1118del - Protein change
- V372fs
- Other names
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- Canonical SPDI
- NC_000016.10:89792033:CCAACCAAC:CCAAC
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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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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 |
4077 | 5203 |
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
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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 (10) |
criteria provided, multiple submitters, no conflicts
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Apr 16, 2024 | RCV000003609.24 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 5, 2024 | RCV000463426.13 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV001091063.24 |
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
(Sep 30, 2015)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia, complementation group A
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000594661.1
First in ClinVar: Aug 27, 2017 Last updated: Aug 27, 2017 |
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Pathogenic
(May 21, 2020)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group A
(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: SCV002768358.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
A heterozygous deletion variant was identified, NM_000135.2(FANCA):c.1115_1118del in exon 13 of 43 of the FANCA gene. (NB: This variant is non-coding in alternative transcripts). This … (more)
A heterozygous deletion variant was identified, NM_000135.2(FANCA):c.1115_1118del in exon 13 of 43 of the FANCA gene. (NB: This variant is non-coding in alternative transcripts). This deletion is predicted to cause a frameshift from amino acid position 372 introducing a stop codon downstream; NP_000126.2(FANCA):p.(Val372Alafs*42), resulting in loss of normal protein function through nonsense-mediated decay (NMD). The variant is present in the gnomAD population database at a global population frequency of 0.0067% (19 heterozygotes, 0 homozygotes) with a European sub-population frequency of 0.014%. The variant has been previously reported in patients with Fanconi anemia (ClinVar, Pilonetto, D. V. et al. (2017), Castella, M. et al . (2011)). Other variants predicted to cause NMD have also been reported as pathogenic in individuals with Fanconi anemia (ClinVar). Based on information available at the time of curation, this variant has been classified as PATHOGENIC. (less)
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Pathogenic
(May 02, 2022)
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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: SCV002781974.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004026680.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
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Pathogenic
(May 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004221907.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
This frameshift variant alters the translational reading frame of the FANCA mRNA and causes the premature termination of FANCA protein synthesis. The frequency of this … (more)
This frameshift variant alters the translational reading frame of the FANCA mRNA and causes the premature termination of FANCA protein synthesis. The frequency of this variant in the general population, 0.0002 (10/50810 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in patients affected with fanconi anemia (PMIDs: 24584348 (2014), 22778927 (2012), 21273304 (2011), 19367192 (2009), 17924555 (2008), 15643609 (2005)). Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jan 05, 2024)
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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: SCV000547753.10
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Val372Alafs*42) in the FANCA gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Val372Alafs*42) in the FANCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). This variant is present in population databases (rs397507552, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 8896564, 15643609, 17924555, 19367192, 21273304, 24584348). This variant is also known as 1159-1162delTTGG. ClinVar contains an entry for this variant (Variation ID: 3440). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 14, 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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Baylor Genetics
Accession: SCV003835075.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Pathogenic
(May 25, 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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GeneDx
Accession: SCV002032553.3
First in ClinVar: Dec 18, 2021 Last updated: Jun 03, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in the heterozygous state in a patient with bone marrow failure syndrome (Perez Botero et al., 2018); This variant is associated with the following publications: (PMID: 31970404, 8896564, 29625052, 26689913, 31589614, 33630411, 33736979, 28104920, 35512711, 34308104, 33718801, 28485484) (less)
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Pathogenic
(Apr 16, 2024)
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criteria provided, single submitter
Method: clinical testing
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Fanconi anemia complementation group A
Affected status: yes
Allele origin:
paternal
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV005016472.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This variant was observed in trans position to a pathogenic complex structural variant of the chromosome 16 inhertied from the mother.
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Pathogenic
(Feb 01, 2020)
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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: SCV001246907.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 2
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Pathogenic
(Nov 01, 1996)
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no assertion criteria provided
Method: literature only
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FANCONI ANEMIA, COMPLEMENTATION GROUP A
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000023767.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 28, 2015 |
Comment on evidence:
In 2 members of a family of British origin with Fanconi anemia (FANCA; 227650), the Fanconi Anaemia/Breast Cancer Consortium (1996) identified a deletion of 1 … (more)
In 2 members of a family of British origin with Fanconi anemia (FANCA; 227650), the Fanconi Anaemia/Breast Cancer Consortium (1996) identified a deletion of 1 of 2 direct repeats of the sequence TTGG at nucleotides 1155-1162 of the FANCA gene. The deletion resulted in a frameshift and the production of a termination codon 42 residues downstream. (less)
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Pathogenic
(Aug 16, 2016)
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no assertion criteria provided
Method: clinical testing
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Fanconi anemia complementation group A
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000485663.2
First in ClinVar: Oct 11, 2015 Last updated: Dec 23, 2019 |
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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: SCV001425645.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
Comment:
Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Daniela Pilonetto, Johan de Winter, Sue Richards.
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Fanconi anemia, group A
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001457963.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Fanconi anemia complementation group A
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000057803.4
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
Comment:
Common in northern Europeans
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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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Fanconi Anemia. | Adam MP | - | 2021 | PMID: 20301575 |
A strategy for molecular diagnostics of Fanconi anemia in Brazilian patients. | Pilonetto DV | Molecular genetics & genomic medicine | 2017 | PMID: 28717661 |
Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology. | De Rocco D | Haematologica | 2014 | PMID: 24584348 |
Diagnosis of Fanconi Anemia: Mutation Analysis by Multiplex Ligation-Dependent Probe Amplification and PCR-Based Sanger Sequencing. | Gille JJ | Anemia | 2012 | PMID: 22778927 |
Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations. | Castella M | Blood | 2011 | PMID: 21273304 |
Validation of Fanconi anemia complementation Group A assignment using molecular analysis. | Moghrabi NN | Genetics in medicine : official journal of the American College of Medical Genetics | 2009 | PMID: 19367192 |
Genetic subtyping of Fanconi anemia by comprehensive mutation screening. | Ameziane N | Human mutation | 2008 | PMID: 17924555 |
Spectrum of sequence variations in the FANCA gene: an International Fanconi Anemia Registry (IFAR) study. | Levran O | Human mutation | 2005 | PMID: 15643609 |
High frequency of large intragenic deletions in the Fanconi anemia group A gene. | Morgan NV | American journal of human genetics | 1999 | PMID: 10521298 |
Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene. | Wijker M | European journal of human genetics : EJHG | 1999 | PMID: 10094191 |
Positional cloning of the Fanconi anaemia group A gene. | Fanconi anaemia/Breast cancer consortium | Nature genetics | 1996 | PMID: 8896564 |
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Text-mined citations for rs397507552 ...
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.