NM_000136.3(FANCC):c.34del (p.Tyr12fs) AND Fanconi anemia

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 3, 2022
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:: RCV004018217.2

Allele description [Variation Report for NM_000136.3(FANCC):c.34del (p.Tyr12fs)]

NM_000136.3(FANCC):c.34del (p.Tyr12fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000136.3(FANCC):c.34del (p.Tyr12fs)

HGVS:

NC_000009.12:g.95249259del
NG_011707.1:g.73452del
NM_000136.3:c.34delMANE SELECT
NM_001243743.2:c.34del
NM_001243744.2:c.34del
NP_000127.2:p.Tyr12Ilefs
NP_000127.2:p.Tyr12fs
NP_001230672.1:p.Tyr12fs
NP_001230673.1:p.Tyr12fs
LRG_497t1:c.33del
LRG_497:g.73452del
LRG_497p1:p.Tyr12Ilefs
NC_000009.11:g.98011541del
NC_000009.12:g.95249258delA
NM_000136.2:c.33delT

Protein change:

Y12fs

Molecular consequence:

NM_000136.3:c.34del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001243743.2:c.34del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001243744.2:c.34del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004848813	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Nov 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004848813

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Nov 3, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848813.1

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

Description

The p.Tyr12IlefsX34 variant in FANCC has not been reported in individuals with Fanconi anemia complementation group C and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 12 and leads to a premature termination codon 34 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the FANCC gene is an established disease mechanism in autosomal recessive Fanconi anemia complementation group C. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Fanconi anemia complementation group C. ACMG/AMP Criteria applied: PM2_supporting, PVS1.

#	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: Jun 23, 2024

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