VCV000974247.12 - ClinVar

NM_000135.4(FANCA):c.2604_2609del

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic
Pathogenic (1); Likely pathogenic (4)

5 out of 6 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000135.4(FANCA):c.2604_2609del

Variation ID: 974247 Accession: VCV000974247.12

Type and length

Microsatellite, 6 bp

Location

Cytogenetic: 16q24.3 16: 89765059-89765064 (GRCh38) [ NCBI UCSC ] 16: 89831467-89831472 (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	Sep 27, 2020	Apr 4, 2026	Feb 18, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000135.4:c.2604_2609del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000135.4:c.2604_2609delTCAGTT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor
NM_000135.3:c.2604_2609delTCAGTT
NC_000016.10:g.89765062TGAAAC[1]
NC_000016.9:g.89831470TGAAAC[1]
NG_011706.1:g.56588TCAGTT[1]
NG_011706.1:g.56594_56599del
LRG_495:g.56588TCAGTT[1]
LRG_495t1:c.2604_2609del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000016.10:89765058:AACTGAAACTGAAAC:AACTGAAAC

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.

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

Links

ClinGen: CA8251619 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.
FANCA		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	5630	7146
LOC130059837	-	-	-	GRCh38	-	172

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.
Fanconi anemia complementation group A	Likely pathogenic (4)	criteria provided, multiple submitters, no conflicts	May 2, 2024	RCV001256500.12
Fanconi anemia	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Feb 18, 2025	RCV001879793.17

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.	Expand all rows Collapse all rows 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.
Likely pathogenic (Dec 15, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Fanconi anemia complementation group A	Department of Pediatrics, Memorial Sloan Kettering Cancer Center Accession: SCV001478119.1 First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021	Publications: PubMed (1) PubMed: 28873162 Observation: 1 Collection method: research Allele origin: germline Affected status: no Observation 1 Collection method: research Allele origin: germline Affected status: no

Likely pathogenic (Nov 29, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Fanconi anemia complementation group A	Baylor Genetics Accession: SCV004196603.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Likely pathogenic (May 02, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Fanconi anemia complementation group A	Fulgent Genetics, Fulgent Genetics Accession: SCV005644470.1 First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Sep 21, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Fanconi anemia	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002218142.5 First in ClinVar: Mar 28, 2022 Last updated: Feb 15, 2026	Publications: PubMed (3) PubMed: 15643609‚ 17924555‚ 29098742 Comment: show This variant, c.2604_2609del, results in the deletion of 2 amino acid(s) of the FANCA protein (p.Gln869_Phe870del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs745864224, gnomAD 0.0009%). This variant has been observed in individual(s) with clinical features of Fanconi anemia (PMID: 15643609, 17924555). ClinVar contains an entry for this variant (Variation ID: 974247). This variant disrupts a region of the FANCA protein in which other variant(s) (p.Gln869Pro) have been determined to be pathogenic (PMID: 15643609, 17924555, 29098742; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely pathogenic (Feb 18, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Natera Variant Classification Schema (03/2026))	Fanconi anemia	Natera, Inc. Accession: SCV007532193.1 First in ClinVar: Apr 04, 2026 Last updated: Apr 04, 2026	Publications: PubMed (2) PubMed: 10090479‚ 17924555 Comment: show The c.2604_2609delTCAGTT variant in FANCA is an in-frame deletion. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 10090479, 17924555). This variant results in a change to the protein length while preserving reading frame, which may disrupt normal protein structure or function. Computational prediction algorithms indicate this variant is likely to affect gene or protein function. Given the available evidence, this variant is classified as Likely Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Feb 28, 2020) N Not contributing to aggregate classification	no assertion criteria provided	Fanconi anemia complementation group A	Leiden Open Variation Database Accession: SCV001425965.1 First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020	Publications: PubMed (1) PubMed: 17924555 Comment: show Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Daniela Pilonetto, Johan de Winter. (less) Observation: 1 Collection method: curation Allele origin: germline Affected status: yes Observation 1 Collection method: curation Allele origin: germline Affected status: yes

Comment:

This variant, c.2604_2609del, results in the deletion of 2 amino acid(s) of the FANCA protein (p.Gln869_Phe870del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs745864224, gnomAD 0.0009%). This variant has been observed in individual(s) with clinical features of Fanconi anemia (PMID: 15643609, 17924555). ClinVar contains an entry for this variant (Variation ID: 974247). This variant disrupts a region of the FANCA protein in which other variant(s) (p.Gln869Pro) have been determined to be pathogenic (PMID: 15643609, 17924555, 29098742; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

Comment:

The c.2604_2609delTCAGTT variant in FANCA is an in-frame deletion. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 10090479, 17924555). This variant results in a change to the protein length while preserving reading frame, which may disrupt normal protein structure or function. Computational prediction algorithms indicate this variant is likely to affect gene or protein function. Given the available evidence, this variant is classified as Likely Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A comprehensive approach to identification of pathogenic FANCA variants in Fanconi anemia patients and their families.	Kimble DC	Human mutation	2018	PMID: 29098742
Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.	Mandelker D	JAMA	2017	PMID: 28873162
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
The FANCA gene in Japanese Fanconi anemia: reports of eight novel mutations and analysis of sequence variability.	Tachibana A	Human mutation	1999	PMID: 10090479

Text-mined citations for this variant ...

Record last updated Jul 15, 2026