NM_000135.4(FANCA):c.2778+1G>A AND Fanconi anemia

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 12, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000811488.9

Allele description [Variation Report for NM_000135.4(FANCA):c.2778+1G>A]

NM_000135.4(FANCA):c.2778+1G>A

Gene:

FANCA:FA complementation group A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000135.4(FANCA):c.2778+1G>A

HGVS:

NC_000016.10:g.89764889C>T
NG_011706.1:g.56769G>A
NM_000135.4:c.2778+1G>AMANE SELECT
NM_001286167.3:c.2778+1G>A
LRG_495t1:c.2778+1G>A
LRG_495:g.56769G>A
NC_000016.9:g.89831297C>T
NM_000135.2:c.2778+1G>A

Links:

dbSNP: rs140180549

NCBI 1000 Genomes Browser:

rs140180549

Molecular consequence:

NM_000135.4:c.2778+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001286167.3:c.2778+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Fanconi anemia (FA)
Synonyms:: Fanconi pancytopenia; Fanconi's anemia
Identifiers:: MONDO: MONDO:0019391; MeSH: D005199; MedGen: C0015625; Orphanet: 84; OMIM: PS227650

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000951756	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 12, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23067021, 24584348, 29098742, 28492532
SCV002092582	Natera, Inc.	no assertion criteria provided	Pathogenic (Jun 2, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000951756

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 12, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002092582

Natera, Inc.

no assertion criteria provided

Pathogenic
(Jun 2, 2021)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

FANCA and FANCG are the major Fanconi anemia genes in the Korean population.

Park J, Chung NG, Chae H, Kim M, Lee S, Kim Y, Lee JW, Cho B, Jeong DC, Park IY.

Clin Genet. 2013 Sep;84(3):271-5. doi: 10.1111/cge.12042.

PubMed [citation]

PMID:: 23067021

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, Bottega R, Cappelli E, Cavani S, Criscuolo M, Nicchia E, Corsolini F, Greco C, Borriello A, Svahn J, Pillon M, Mecucci C, Casazza G, Verzegnassi F, Cugno C, Locasciulli A, Farruggia P, Longoni D, Ramenghi U, Barberi W, Tucci F, Perrotta S, et al.

Haematologica. 2014 Jun;99(6):1022-31. doi: 10.3324/haematol.2014.104224. Epub 2014 Feb 28. Erratum in: Haematologica. 2014 Sep;99(9):1532.

PubMed [citation]

PMID:: 24584348
PMCID:: PMC4040906

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000951756.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002092582.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 12, 2024

ClinVar

Relating variation to medicine