NM_000136.3(FANCC):c.1272G>A (p.Trp424Ter) AND Fanconi anemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 24, 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:: RCV003635959.2

Allele description [Variation Report for NM_000136.3(FANCC):c.1272G>A (p.Trp424Ter)]

NM_000136.3(FANCC):c.1272G>A (p.Trp424Ter)

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.1272G>A (p.Trp424Ter)

HGVS:

NC_000009.12:g.95111520C>T
NG_011707.1:g.211190G>A
NM_000136.3:c.1272G>AMANE SELECT
NM_001243743.2:c.1272G>A
NM_001243744.2:c.1272G>A
NP_000127.2:p.Trp424Ter
NP_001230672.1:p.Trp424Ter
NP_001230673.1:p.Trp424Ter
LRG_497t1:c.1272G>A
LRG_497:g.211190G>A
NC_000009.11:g.97873802C>T
NM_000136.2:c.1272G>A

Protein change:

W424*

Links:

dbSNP: rs2134548133

NCBI 1000 Genomes Browser:

rs2134548133

Molecular consequence:

NM_000136.3:c.1272G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001243743.2:c.1272G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001243744.2:c.1272G>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004487806	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 24, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17924555, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004487806

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 24, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic subtyping of Fanconi anemia by comprehensive mutation screening.

Ameziane N, Errami A, Léveillé F, Fontaine C, de Vries Y, van Spaendonk RM, de Winter JP, Pals G, Joenje H.

Hum Mutat. 2008 Jan;29(1):159-66.

PubMed [citation]

PMID:: 17924555

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004487806.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Trp424*) in the FANCC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1050046). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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