ClinVar Genomic variation as it relates to human health
NM_000135.4(FANCA):c.2778+1G>A
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.2778+1G>A
Variation ID: 635518 Accession: VCV000635518.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16q24.3 16: 89764889 (GRCh38) [ NCBI UCSC ] 16: 89831297 (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 Jul 15, 2019 May 12, 2024 Sep 12, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000135.4:c.2778+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001286167.3:c.2778+1G>A splice donor NC_000016.10:g.89764889C>T NC_000016.9:g.89831297C>T NG_011706.1:g.56769G>A LRG_495:g.56769G>A LRG_495t1:c.2778+1G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000016.10:89764888:C:T
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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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00002
- Links
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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FANCA | - | - |
GRCh38 GRCh37 |
4075 | 5199 |
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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Jul 28, 2023 | RCV000786986.7 | |
Pathogenic (2) |
criteria provided, single submitter
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Sep 12, 2023 | RCV000811488.9 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 1, 2023 | RCV002269312.9 |
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
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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
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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
(Feb 02, 2022)
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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: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002768139.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Fanconi anemia of complementation group A (MIM#227650). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v3: 3 heterozygotes, 0 homozygotes). (SP) 0311 - An alternative nucleotide change at the same canonical splice site, is present in gnomAD (v2) at a frequency of 0.00000398 (c.2778+1G>T: 1 heterozygote, 0 homozygotes). (SB) 0508 - In silico predictions for abnormal splicing are inconclusive. While NetGene2 predicted a loss of the WT donor site, Fruitfly did not predict the presence of a WT donor site. It should also be noted that the affected nucleotide is highly conserved. (I) 0702 - Other canonical splice variants comparable to the one identified in this case have strong previous evidence for pathogenicity. The c.2778+1G>C variant was identified in one individual with Fanconi anemia-associated bone marrow failure and classified as pathogenic by one clinical diagnostic laboratory, while c.2778+1G>T was reported in one individual with Fanconi anemia (PMIDs: 23067021, 28717661, ClinVar). Additionally, c.2778+2T>C was identified in one individual with Fanconi anemia and has been classified as likely pathogenic and pathogenic by two clinical diagnostic laboratories (PMID: 31558676, ClinVar). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been reported as compound heterozygous in two individuals with Fanconi anemia and has been classified as pathogenic by clinical diagnostic laboratories (PMIDs: 24584348, 29098742, ClinVar). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Pathogenic
(Jul 24, 2022)
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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: SCV002552606.2
First in ClinVar: Jul 29, 2022 Last updated: Mar 04, 2023 |
Comment:
Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is … (more)
Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 29753700, 29098742, 24584348) (less)
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Pathogenic
(Jul 28, 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: SCV004196066.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Sep 12, 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: SCV000951756.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 28, … (more)
For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 28, but is expected to preserve the integrity of the reading-frame (PMID: 24584348). ClinVar contains an entry for this variant (Variation ID: 635518). Disruption of this splice site has been observed in individuals with Fanconi anemia (PMID: 23067021, 24584348, 29098742). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change affects a donor splice site in intron 28 of the FANCA gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. (less)
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Pathogenic
(Jun 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004010536.7
First in ClinVar: Jul 16, 2023 Last updated: May 12, 2024 |
Comment:
FANCA: PVS1, PM2, PS3:Moderate
Number of individuals with the variant: 1
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Pathogenic
(Nov 23, 2018)
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no assertion criteria provided
Method: clinical testing
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Fanconi anemia complementation group A
Affected status: yes
Allele origin:
germline
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Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare
Accession: SCV000925892.1
First in ClinVar: Jul 15, 2019 Last updated: Jul 15, 2019 |
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Uncertain significance
(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: SCV001426095.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
Comment:
Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.
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Pathogenic
(Jun 02, 2021)
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no assertion criteria provided
Method: clinical testing
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Fanconi anemia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002092582.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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Characterization and genotype-phenotype correlation of patients with Fanconi anemia in a multi-ethnic population. | Steinberg-Shemer O | Haematologica | 2020 | PMID: 31558676 |
A comprehensive approach to identification of pathogenic FANCA variants in Fanconi anemia patients and their families. | Kimble DC | Human mutation | 2018 | PMID: 29098742 |
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 |
FANCA and FANCG are the major Fanconi anemia genes in the Korean population. | Park J | Clinical genetics | 2013 | PMID: 23067021 |
Text-mined citations for rs140180549 ...
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.