VCV000435129.18 - ClinVar

NM_000135.4(FANCA):c.2398G>T (p.Glu800Ter)

Germline

Classification

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

Pathogenic

2 out of 4 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.2398G>T (p.Glu800Ter)

Variation ID: 435129 Accession: VCV000435129.18

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16q24.3 16: 89769943 (GRCh38) [ NCBI UCSC ] 16: 89836351 (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	Aug 28, 2017	Feb 15, 2026	May 15, 2018

HGVS

Nucleotide	Protein	Molecular consequence
NM_000135.4:c.2398G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000126.2:p.Glu800Ter	nonsense
NM_001286167.3:c.2398G>T	NP_001273096.1:p.Glu800Ter	nonsense
NC_000016.10:g.89769943C>A
NC_000016.9:g.89836351C>A
NG_011706.1:g.51715G>T
LRG_495:g.51715G>T
LRG_495t1:c.2398G>T

... more HGVS ... less HGVS

Protein change

E800*

Other names

Canonical SPDI

NC_000016.10:89769942:C:A

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: CA397443878 dbSNP: rs1555547474 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	5499	6992

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	Pathogenic (2)	criteria provided, single submitter	Jul 7, 2016	RCV000499975.8
Fanconi anemia	Pathogenic (2)	criteria provided, single submitter	May 15, 2018	RCV001380594.11

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.
Pathogenic (Jul 07, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Fanconi anemia, complementation group A	Genetic Services Laboratory, University of Chicago Accession: SCV000594657.1 First in ClinVar: Aug 28, 2017 Last updated: Aug 28, 2017	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (May 15, 2018) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Fanconi anemia	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001578707.5 First in ClinVar: May 10, 2021 Last updated: Feb 15, 2026	Publications: PubMed (1) PubMed: 19367192 Comment: show Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). This variant has not been reported in the literature in individuals with FANCA-related disease. ClinVar contains an entry for this variant (Variation ID: 435129). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu800*) in the FANCA gene. It is expected to result in an absent or disrupted protein product. 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 (Dec 18, 2017) N Not contributing to aggregate classification	no assertion criteria provided	Fanconi anemia complementation group A	Counsyl Accession: SCV000796397.3 First in ClinVar: Aug 28, 2017 Last updated: Jun 29, 2025	Comment: show This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (May 14, 2021) N Not contributing to aggregate classification	no assertion criteria provided	Fanconi anemia	Natera, Inc. Accession: SCV002092609.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). This variant has not been reported in the literature in individuals with FANCA-related disease. ClinVar contains an entry for this variant (Variation ID: 435129). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu800*) in the FANCA gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
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

Text-mined citations for rs1555547474 ...

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 Feb 15, 2026