NM_000136.3(FANCC):c.1330-2A>C AND Fanconi anemia

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 14, 2021
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:: RCV002050320.4

Allele description [Variation Report for NM_000136.3(FANCC):c.1330-2A>C]

NM_000136.3(FANCC):c.1330-2A>C

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.1330-2A>C

HGVS:

NC_000009.12:g.95107271T>G
NG_011707.1:g.215439A>C
NG_027833.2:g.385574T>G
NM_000136.3:c.1330-2A>CMANE SELECT
NM_001243743.2:c.1330-2A>C
LRG_497:g.215439A>C
NC_000009.11:g.97869553T>G

Links:

dbSNP: rs2134456820

NCBI 1000 Genomes Browser:

rs2134456820

Molecular consequence:

NM_000136.3:c.1330-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001243743.2:c.1330-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

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CBY1-interacting BAR domain-containing protein 1 isoform 1 [Mus musculus]
CBY1-interacting BAR domain-containing protein 1 isoform 1 [Mus musculus]
gi|158749636|ref|NP_080834.3|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002317562	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 14, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 17924555, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002317562

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 14, 2021)

germline

clinical testing

PubMed (3)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002317562.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change affects an acceptor splice site in intron 13 of the FANCC gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with FANCC-related conditions. This variant is not present in population databases (ExAC no frequency).

#	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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