NM_000135.4(FANCA):c.2557C>T (p.Arg853Ter) AND Fanconi anemia

Clinical significance:Pathogenic (Last evaluated: Feb 26, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000630944.3

Allele description [Variation Report for NM_000135.4(FANCA):c.2557C>T (p.Arg853Ter)]

NM_000135.4(FANCA):c.2557C>T (p.Arg853Ter)

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.2557C>T (p.Arg853Ter)
HGVS:
  • NC_000016.10:g.89767185G>A
  • NG_011706.1:g.54473C>T
  • NM_000135.4:c.2557C>TMANE SELECT
  • NM_001286167.3:c.2557C>T
  • NP_000126.2:p.Arg853Ter
  • NP_001273096.1:p.Arg853Ter
  • LRG_495t1:c.2557C>T
  • LRG_495:g.54473C>T
  • NC_000016.9:g.89833593G>A
  • NM_000135.2:c.2557C>T
Protein change:
R853*; ARG853TER
Links:
OMIM: 607139.0011; dbSNP: rs752160950
NCBI 1000 Genomes Browser:
rs752160950
Molecular consequence:
  • NM_000135.4:c.2557C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001286167.3:c.2557C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000751919Invitaecriteria provided, single submitter
Pathogenic
(Feb 26, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

A rapid method for retrovirus-mediated identification of complementation groups in Fanconi anemia patients.

Chandra S, Levran O, Jurickova I, Maas C, Kapur R, Schindler D, Henry R, Milton K, Batish SD, Cancelas JA, Hanenberg H, Auerbach AD, Williams DA.

Mol Ther. 2005 Nov;12(5):976-84. Epub 2005 Aug 9.

PubMed [citation]
PMID:
16084127

Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M.

Singh TR, Bakker ST, Agarwal S, Jansen M, Grassman E, Godthelp BC, Ali AM, Du CH, Rooimans MA, Fan Q, Wahengbam K, Steltenpool J, Andreassen PR, Williams DA, Joenje H, de Winter JP, Meetei AR.

Blood. 2009 Jul 2;114(1):174-80. doi: 10.1182/blood-2009-02-207811. Epub 2009 May 7.

PubMed [citation]
PMID:
19423727
PMCID:
PMC2710946
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000751919.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Arg853*) in the FANCA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs752160950, ExAC 0.01%). This variant has been reported in one individual affected with Fanconi anemia (PMID: 16084127). In addition, this variant has been observed on the opposite chromosome (in trans) from another pathogenic FANCA variant in two siblings affected with Fanconi anemia (PMID: 19423727). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 192384). An experimental study has shown that lymphoblasts harboring this nonsense change and another pathogenic FANCA variant are defective in FANCD2 monoubiquitination (PMID: 19423727). Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 6, 2021

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