NM_000136.3(FANCC):c.1628C>A (p.Ser543Ter) AND Fanconi anemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 7, 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:: RCV001059596.8

Allele description [Variation Report for NM_000136.3(FANCC):c.1628C>A (p.Ser543Ter)]

NM_000136.3(FANCC):c.1628C>A (p.Ser543Ter)

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.1628C>A (p.Ser543Ter)

HGVS:

NC_000009.12:g.95101756G>T
NG_011707.1:g.220954C>A
NM_000136.3:c.1628C>AMANE SELECT
NM_001243743.2:c.1628C>A
NP_000127.2:p.Ser543Ter
NP_001230672.1:p.Ser543Ter
LRG_497t1:c.1628C>A
LRG_497:g.220954C>A
NC_000009.11:g.97864038G>T
NM_000136.2:c.1628C>A

Protein change:

S543*

Links:

dbSNP: rs867319477

NCBI 1000 Genomes Browser:

rs867319477

Molecular consequence:

NM_000136.3:c.1628C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001243743.2:c.1628C>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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LOC107482396 [Arachis duranensis]
LOC107482396 [Arachis duranensis]
Gene ID:107482396

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001224223	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 7, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8103176, 8882868, 24584348, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001224223

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 7, 2019)

germline

clinical testing

PubMed (4)
[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

FACC gene mutations and early prenatal diagnosis of Fanconi's anaemia.

Murer-Orlando M, Llerena JC Jr, Birjandi F, Gibson RA, Mathew CG.

Lancet. 1993 Sep 11;342(8872):686. No abstract available.

PubMed [citation]

PMID:: 8103176

Sequence variations in the Fanconi anaemia gene, FAC: pathogenicity of 1806insA and R548X and recognition of D195V as a polymorphic variant.

Lo ten Foe JR, Barel MT, Thuss P, Digweed M, Arwert F, Joenje H.

Hum Genet. 1996 Nov;98(5):522-3.

PubMed [citation]

PMID:: 8882868

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001224223.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change results in a premature translational stop signal in the FANCC gene (p.Ser543*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acids of the FANCC protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the FANCC protein. Other variant(s) that disrupt this region (p.Arg548*) have been determined to be pathogenic (PMID: 8103176, 8882868, 24584348). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has not been reported in the literature in individuals with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 370412). 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: Oct 13, 2024

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