NM_000136.3(FANCC):c.165+1G>T AND Fanconi anemia

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 18, 2019
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:: RCV001221363.3

Allele description [Variation Report for NM_000136.3(FANCC):c.165+1G>T]

NM_000136.3(FANCC):c.165+1G>T

Gene:

FANCC:FA complementation group C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000136.3(FANCC):c.165+1G>T

HGVS:

NC_000009.12:g.95249126C>A
NG_011707.1:g.73584G>T
NM_000136.3:c.165+1G>TMANE SELECT
NM_001243743.2:c.165+1G>T
NM_001243744.2:c.165+1G>T
LRG_497t1:c.165+1G>T
LRG_497:g.73584G>T
NC_000009.11:g.98011408C>A
NM_000136.2:c.165+1G>T

Nucleotide change:

IVS2DS, G-T, +1

Links:

OMIM: 613899.0009; dbSNP: rs794726668

NCBI 1000 Genomes Browser:

rs794726668

Molecular consequence:

NM_000136.3:c.165+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001243743.2:c.165+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001243744.2:c.165+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV001393403	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 18, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20869034, 17924555, 28492532
SCV002081302	Natera, Inc.	no assertion criteria provided	Pathogenic (Mar 17, 2017)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001393403

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 18, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002081302

Natera, Inc.

no assertion criteria provided

Pathogenic
(Mar 17, 2017)

germline

clinical testing

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

Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs.

Hartmann L, Neveling K, Borkens S, Schneider H, Freund M, Grassman E, Theiss S, Wawer A, Burdach S, Auerbach AD, Schindler D, Hanenberg H, Schaal H.

Am J Hum Genet. 2010 Oct 8;87(4):480-93. doi: 10.1016/j.ajhg.2010.08.016.

PubMed [citation]

PMID:: 20869034
PMCID:: PMC2948791

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 Invitae, SCV001393403.1

#	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 a donor splice site in intron 2 of the FANCC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another FANCC variant in individuals affected with Fanconi anemia and to segregate with disease in families (PMID: 20869034). ClinVar contains an entry for this variant (Variation ID: 12051). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 20869034). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). 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

From Natera, Inc., SCV002081302.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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: May 7, 2024

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