U.S. flag

An official website of the United States government

NM_001018115.3(FANCD2):c.205+1G>A AND Fanconi anemia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 12, 2021
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:
RCV002030604.4

Allele description [Variation Report for NM_001018115.3(FANCD2):c.205+1G>A]

NM_001018115.3(FANCD2):c.205+1G>A

Genes:
LOC107303338:3p25 FANCD2 Alu-mediated recombination region [Gene]
FANCD2:FA complementation group D2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p25.3
Genomic location:
Preferred name:
NM_001018115.3(FANCD2):c.205+1G>A
HGVS:
  • NC_000003.12:g.10032973G>A
  • NG_007311.1:g.11545G>A
  • NG_046754.1:g.2127G>A
  • NM_001018115.3:c.205+1G>AMANE SELECT
  • NM_001319984.2:c.205+1G>A
  • NM_001374253.1:c.205+1G>A
  • NM_001374254.1:c.205+1G>A
  • NM_001374255.1:c.205+1G>A
  • NM_033084.6:c.205+1G>A
  • LRG_306:g.11545G>A
  • NC_000003.11:g.10074657G>A
Links:
dbSNP: rs2124970985
NCBI 1000 Genomes Browser:
rs2124970985
Molecular consequence:
  • NM_001018115.3:c.205+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001319984.2:c.205+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374253.1:c.205+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374254.1:c.205+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001374255.1:c.205+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_033084.6:c.205+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

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002269644Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Aug 12, 2021) 		germlineclinical testing

PubMed (3)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Hypomorphic mutations in the gene encoding a key Fanconi anemia protein, FANCD2, sustain a significant group of FA-D2 patients with severe phenotype.

Kalb R, Neveling K, Hoehn H, Schneider H, Linka Y, Batish SD, Hunt C, Berwick M, Callen E, Surralles J, Casado JA, Bueren J, Dasi A, Soulier J, Gluckman E, Zwaan CM, van Spaendonk R, Pals G, de Winter JP, Joenje H, Grompe M, Auerbach AD, et al.

Am J Hum Genet. 2007 May;80(5):895-910. Epub 2007 Apr 6. Erratum in: Am J Hum Genet. 2007 Jul;81(1):196.

PubMed [citation]
PMID:
17436244
PMCID:
PMC1852747
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002269644.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change affects a donor splice site in intron 3 of the FANCD2 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 FANCD2 are known to be pathogenic (PMID: 17436244). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2024