NM_000136.3(FANCC):c.489_490del (p.Asn164fs) AND Fanconi anemia complementation group C

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: May 10, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000984173.5

Allele description [Variation Report for NM_000136.3(FANCC):c.489_490del (p.Asn164fs)]

NM_000136.3(FANCC):c.489_490del (p.Asn164fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000136.3(FANCC):c.489_490del (p.Asn164fs)

HGVS:

NC_000009.11:g.97933392_97933393del
NC_000009.12:g.95171111CT[2]
NG_011707.1:g.151595GA[2]
NM_000136.3:c.489_490delMANE SELECT
NM_001243743.2:c.489_490del
NM_001243744.2:c.489_490del
NP_000127.2:p.Asn164fs
NP_001230672.1:p.Asn164fs
NP_001230673.1:p.Asn164fs
LRG_497t1:c.489_490del
LRG_497:g.151595GA[2]
NC_000009.11:g.97933392_97933393del
NC_000009.11:g.97933393CT[2]
NC_000009.11:g.97933397_97933398delCT
NM_000136.2:c.489_490del
NM_000136.2:c.489_490delGA

Protein change:

N164fs

Links:

dbSNP: rs730881708

NCBI 1000 Genomes Browser:

rs730881708

Molecular consequence:

NM_000136.3:c.489_490del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001243743.2:c.489_490del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001243744.2:c.489_490del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Fanconi anemia complementation group C (FANCC)
Synonyms:: FANCONI PANCYTOPENIA, TYPE 3; FACC; Fanconi anemia, group C
Identifiers:: MONDO: MONDO:0009213; MedGen: C3468041; Orphanet: 84; OMIM: 227645

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LMNB1-DT LMNB1 divergent transcript [Homo sapiens]
LMNB1-DT LMNB1 divergent transcript [Homo sapiens]
Gene ID:102723557

Gene
LMNB1-DT AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001132188	Counsyl	no assertion criteria provided	Likely pathogenic (Oct 15, 2015)	unknown	clinical testing
SCV001163627	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001365298	Leiden Open Variation Database	no assertion criteria provided	Pathogenic (Feb 28, 2020)	germline	curation
SCV001821465	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Aug 8, 2021)	germline	clinical testing	Citation Link,
SCV002806818	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 10, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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 Counsyl, SCV001132188.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV001163627.1

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

#	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 Leiden Open Variation Database, SCV001365298.1

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

Description

Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001821465.1

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

Description

Variant summary: FANCC c.489_490delGA (p.Asn164SerfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251214 control chromosomes. To our knowledge, no occurrence of c.489_490delGA in individuals affected with Fanconi Anemia Group C and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely 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 Fulgent Genetics, Fulgent Genetics, SCV002806818.1

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

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

Last Updated: Sep 29, 2024

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