U.S. flag

An official website of the United States government

NM_000135.4(FANCA):c.4199G>C (p.Arg1400Pro) AND Fanconi anemia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 14, 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:
RCV001858712.6

Allele description [Variation Report for NM_000135.4(FANCA):c.4199G>C (p.Arg1400Pro)]

NM_000135.4(FANCA):c.4199G>C (p.Arg1400Pro)

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.4199G>C (p.Arg1400Pro)
HGVS:
  • NC_000016.10:g.89738943C>G
  • NG_011706.1:g.82715G>C
  • NM_000135.4:c.4199G>CMANE SELECT
  • NM_001113525.2:c.*697C>GMANE SELECT
  • NM_001286167.3:c.4203G>C
  • NM_152287.4:c.*697C>G
  • NP_000126.2:p.Arg1400Pro
  • NP_000126.2:p.Arg1400Pro
  • NP_001273096.1:p.Ser1401=
  • LRG_495t1:c.4199G>C
  • LRG_495:g.82715G>C
  • LRG_495p1:p.Arg1400Pro
  • NC_000016.9:g.89805351C>G
  • NM_000135.2:c.4199G>C
  • NR_110122.2:n.2697C>G
  • NR_110126.2:n.2580C>G
  • NR_110128.2:n.2520C>G
  • NR_110129.2:n.2614C>G
Protein change:
R1400P
Links:
dbSNP: rs149851163
NCBI 1000 Genomes Browser:
rs149851163
Molecular consequence:
  • NM_001113525.2:c.*697C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_152287.4:c.*697C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000135.4:c.4199G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_110122.2:n.2697C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110126.2:n.2580C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110128.2:n.2520C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110129.2:n.2614C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001286167.3:c.4203G>C - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV002111612Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jun 14, 2023) 		germlineclinical testing

PubMed (9)
[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

Spectrum of sequence variations in the FANCA gene: an International Fanconi Anemia Registry (IFAR) study.

Levran O, Diotti R, Pujara K, Batish SD, Hanenberg H, Auerbach AD.

Hum Mutat. 2005 Feb;25(2):142-9.

PubMed [citation]
PMID:
15643609

Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations.

Castella M, Pujol R, Callén E, Trujillo JP, Casado JA, Gille H, Lach FP, Auerbach AD, Schindler D, Benítez J, Porto B, Ferro T, Muñoz A, Sevilla J, Madero L, Cela E, Beléndez C, de Heredia CD, Olivé T, de Toledo JS, Badell I, Torrent M, et al.

Blood. 2011 Apr 7;117(14):3759-69. doi: 10.1182/blood-2010-08-299917. Epub 2011 Jan 27.

PubMed [citation]
PMID:
21273304
PMCID:
PMC3083295
See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002111612.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

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. This variant disrupts the p.Arg1400 amino acid residue in FANCA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15643609, 21273304, 24584348, 28102861, 28717661, 29098742). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FANCA protein function. ClinVar contains an entry for this variant (Variation ID: 803290). This missense change has been observed in individuals with Fanconi anemia (PMID: 28717661, 30792206, 34585473). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1400 of the FANCA protein (p.Arg1400Pro).

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

Last Updated: Sep 29, 2024