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

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Oct 31, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000173013.5

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, complementation group A (FANCA)
Synonyms:
Fanconi anemia, group A
Identifiers:
MONDO: MONDO:0009215; MedGen: C3469521; Orphanet: 84; OMIM: 227650

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000224032OMIMno assertion criteria providedPathogenic
(Jul 2, 2009)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000795425Counsylcriteria provided, single submitter
Likely pathogenic
(Nov 22, 2017)
unknownclinical testing

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

Citation Link,

SCV000894103Fulgent Genetics,Fulgent Geneticscriteria provided, single submitter
Pathogenic
(Oct 31, 2018)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M.

Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, Steltenpool J, Stone S, Dokal I, Mathew CG, Hoatlin M, Joenje H, de Winter JP, Wang W.

Nat Genet. 2005 Sep;37(9):958-63. Epub 2005 Aug 21.

PubMed [citation]
PMID:
16116422
PMCID:
PMC2704909

DNA helicases FANCM and DDX11 are determinants of PARP inhibitor sensitivity.

Stoepker C, Faramarz A, Rooimans MA, van Mil SE, Balk JA, Velleuer E, Ameziane N, Te Riele H, de Winter JP.

DNA Repair (Amst). 2015 Feb;26:54-64. doi: 10.1016/j.dnarep.2014.12.003. Epub 2014 Dec 24.

PubMed [citation]
PMID:
25583207
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000224032.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a cell line derived from a proband with Fanconi anemia of complementation group A (FANCA; 227650), Singh et al. (2009) identified compound heterozygous mutations in the FANCA gene: a c.2557C-T transition, resulting in an arg853-to-ter (R853X) substitution, and a G-to-A transition in intron 7 (IVS7+5G-A; 607139.0012), resulting in a 30-bp insertion in the FANCA mRNA, which adds 10 amino acids between residues 236 and 237 of the protein. Expression of the mutant FANCA protein was unable to restore FANDC2 monoubiquitination in FANCA-deficient lymphoblasts, demonstrating that the splice site mutation is pathogenic. Each unaffected parent was heterozygous for 1 of the mutations. This patient had a sib (EUFA867) who had no clinical symptoms of Fanconi anemia but whose cell lines carried the same biallelic FANCA mutations. Both patients were originally reported by Meetei et al. (2005) as having Fanconi anemia, complementation group M due to compound heterozygous mutations in the FAAP250 gene (FANCM; 609644). However, Singh et al. (2009) stated that the proband only carried 1 of the FAAP250 mutations, which in retrospect reclassified this patient as having FANCA. The clinically unaffected sib carried both biallelic mutations in the FANCA gene and biallelic variants in the FAAP250 gene (see 609644.0001 and 609644.0002).

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

From Counsyl, SCV000795425.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Fulgent Genetics,Fulgent Genetics, SCV000894103.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 6, 2021

Support Center