NM_000136.3(FANCC):c.1661T>C (p.Leu554Pro) AND Fanconi anemia

Clinical significance:Pathogenic (Last evaluated: Jul 23, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001221431.2

Allele description [Variation Report for NM_000136.3(FANCC):c.1661T>C (p.Leu554Pro)]

NM_000136.3(FANCC):c.1661T>C (p.Leu554Pro)

Genes:
FANCC:FA complementation group C [Gene - OMIM - HGNC]
AOPEP:aminopeptidase O (putative) [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q22.32
Genomic location:
Preferred name:
NM_000136.3(FANCC):c.1661T>C (p.Leu554Pro)
HGVS:
  • NC_000009.12:g.95101723A>G
  • NG_011707.1:g.220987T>C
  • NM_000136.3:c.1661T>CMANE SELECT
  • NM_001243743.2:c.1661T>C
  • NP_000127.2:p.Leu554Pro
  • NP_000127.2:p.Leu554Pro
  • NP_000127.2:p.Leu554Pro
  • NP_001230672.1:p.Leu554Pro
  • LRG_497t1:c.1661T>C
  • LRG_497:g.220987T>C
  • LRG_497p1:p.Leu554Pro
  • NC_000009.11:g.97864005A>G
  • NM_000136.2:c.1661T>C
  • Q00597:p.Leu554Pro
Protein change:
L554P; LEU554PRO
Links:
UniProtKB: Q00597#VAR_005233; OMIM: 613899.0001; dbSNP: rs104886458
NCBI 1000 Genomes Browser:
rs104886458
Molecular consequence:
  • NM_000136.3:c.1661T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243743.2:c.1661T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001393476Invitaecriteria provided, single submitter
Pathogenic
(Jul 23, 2020)
germlineclinical testing

PubMed (6)
[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

The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex.

Garcia-Higuera I, Kuang Y, Denham J, D'Andrea AD.

Blood. 2000 Nov 1;96(9):3224-30.

PubMed [citation]
PMID:
11050007

Positive diepoxybutane test in only one of two brothers found to be compound heterozygotes for Fanconi's anaemia complementation group C mutations.

Dokal I, Chase A, Morgan NV, Coulthard S, Hall G, Mathew CG, Roberts I.

Br J Haematol. 1996 Jun;93(4):813-6.

PubMed [citation]
PMID:
8703809
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV001393476.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces leucine with proline at codon 554 of the FANCC protein (p.Leu554Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs104886458, ExAC 0.002%). This variant has been observed in individual(s) with Fanconi anemia (PMID: 11050007, 8703809). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 12043). This variant has been reported to affect FANCC protein function (PMID: 8613549, 9398857, 9242535). 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: Nov 20, 2021

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