NM_000135.4(FANCA):c.4015del (p.Leu1339fs) AND Fanconi anemia

Clinical significance:Pathogenic (Last evaluated: Oct 13, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001043860.2

Allele description [Variation Report for NM_000135.4(FANCA):c.4015del (p.Leu1339fs)]

NM_000135.4(FANCA):c.4015del (p.Leu1339fs)

Genes:
FANCA:FA complementation group A [Gene - OMIM - HGNC]
ZNF276:zinc finger protein 276 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
16q24.3
Genomic location:
Preferred name:
NM_000135.4(FANCA):c.4015del (p.Leu1339fs)
HGVS:
  • NC_000016.10:g.89739285del
  • NG_011706.1:g.82373del
  • NM_000135.4:c.4015delMANE SELECT
  • NM_001113525.2:c.*1039delMANE SELECT
  • NM_001286167.3:c.4015del
  • NM_152287.4:c.*1039del
  • NP_000126.2:p.Leu1339fs
  • NP_001273096.1:p.Leu1339fs
  • LRG_495t1:c.4015del
  • LRG_495:g.82373del
  • NC_000016.9:g.89805693del
  • NM_000135.2:c.4015delC
  • NR_110122.2:n.3039del
  • NR_110126.2:n.2922del
  • NR_110128.1:n.2862del
  • NR_110129.2:n.2956del
Protein change:
L1339fs
Links:
dbSNP: rs762902309
NCBI 1000 Genomes Browser:
rs762902309
Molecular consequence:
  • NM_001113525.2:c.*1039del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_152287.4:c.*1039del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000135.4:c.4015del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001286167.3:c.4015del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_110122.2:n.3039del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110126.2:n.2922del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110128.1:n.2862del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_110129.2:n.2956del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV001207627Invitaecriteria provided, single submitter
Pathogenic
(Oct 13, 2020)
germlineclinical testing

PubMed (5)
[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

High frequency of large intragenic deletions in the Fanconi anemia group A gene.

Morgan NV, Tipping AJ, Joenje H, Mathew CG.

Am J Hum Genet. 1999 Nov;65(5):1330-41.

PubMed [citation]
PMID:
10521298
PMCID:
PMC1288285

Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapy.

Ellingson MS, Hart SN, Kalari KR, Suman V, Schahl KA, Dockter TJ, Felten SJ, Sinnwell JP, Thompson KJ, Tang X, Vedell PT, Barman P, Sicotte H, Eckel-Passow JE, Northfelt DW, Gray RJ, McLaughlin SA, Moreno-Aspitia A, Ingle JN, Moyer AM, Visscher DW, Jones K, et al.

Breast Cancer Res Treat. 2015 Sep;153(2):435-43. doi: 10.1007/s10549-015-3545-6. Epub 2015 Aug 22.

PubMed [citation]
PMID:
26296701
PMCID:
PMC4559569
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001207627.2

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

Description

This sequence change creates a premature translational stop signal (p.Leu1339Serfs*24) in the FANCA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs762902309, ExAC 0.002%). This variant has been observed in combination with another FANCA variant in individuals affected with Fanconi anemia or as heterozygous in an individual affected with breast cancer (PMID: 10521298, 26296701, 29098742). ClinVar contains an entry for this variant (Variation ID: 208638). 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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