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NM_000135.4(FANCA):c.4168-1G>A AND Fanconi anemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 20, 2022
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:
RCV003017434.2

Allele description [Variation Report for NM_000135.4(FANCA):c.4168-1G>A]

NM_000135.4(FANCA):c.4168-1G>A

Genes:
FANCA:FA complementation group A [Gene - OMIM - HGNC]
ZNF276:zinc finger protein 276 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q24.3
Genomic location:
Preferred name:
NM_000135.4(FANCA):c.4168-1G>A
HGVS:
  • NC_000016.10:g.89738975C>T
  • NG_011706.1:g.82683G>A
  • NM_000135.4:c.4168-1G>AMANE SELECT
  • NM_001113525.2:c.*729C>TMANE SELECT
  • NM_001286167.3:c.4172-1G>A
  • NM_152287.4:c.*729C>T
  • LRG_495:g.82683G>A
  • NC_000016.9:g.89805383C>T
  • NR_110122.2:n.2729C>T
  • NR_110126.2:n.2612C>T
  • NR_110128.2:n.2552C>T
  • NR_110129.2:n.2646C>T
Molecular consequence:
  • NM_001113525.2:c.*729C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_152287.4:c.*729C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NR_110122.2:n.2729C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110126.2:n.2612C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110128.2:n.2552C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110129.2:n.2646C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000135.4:c.4168-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001286167.3:c.4172-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003325377Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 20, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification and characterization of novel mutations of the major Fanconi anemia gene FANCA in the Japanese population.

Yagasaki H, Hamanoue S, Oda T, Nakahata T, Asano S, Yamashita T.

Hum Mutat. 2004 Dec;24(6):481-90.

PubMed [citation]
PMID:
15523645

Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes.

Muramatsu H, Okuno Y, Yoshida K, Shiraishi Y, Doisaki S, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Takahashi Y, Kanno H, Yamaguchi H, Ohga S, Manabe A, Harigae H, Kunishima S, Ishii E, et al.

Genet Med. 2017 Jul;19(7):796-802. doi: 10.1038/gim.2016.197. Epub 2017 Jan 19.

PubMed [citation]
PMID:
28102861
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003325377.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individuals with Fanconi anemia (PMID: 15523645, 28102861). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 41 of the FANCA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 1, 2024