NM_000136.3(FANCC):c.1069C>T (p.Gln357Ter) AND not provided

Clinical significance:Pathogenic (Last evaluated: Apr 12, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000483955.3

Allele description [Variation Report for NM_000136.3(FANCC):c.1069C>T (p.Gln357Ter)]

NM_000136.3(FANCC):c.1069C>T (p.Gln357Ter)

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.1069C>T (p.Gln357Ter)
HGVS:
  • NC_000009.12:g.95117318G>A
  • NG_011707.1:g.205392C>T
  • NM_000136.3:c.1069C>TMANE SELECT
  • NM_001243743.2:c.1069C>T
  • NM_001243744.2:c.1069C>T
  • NP_000127.2:p.Gln357Ter
  • NP_001230672.1:p.Gln357Ter
  • NP_001230673.1:p.Gln357Ter
  • LRG_497t1:c.1069C>T
  • LRG_497:g.205392C>T
  • NC_000009.11:g.97879600G>A
  • NM_000136.2:c.1069C>T
Protein change:
Q357*
Links:
dbSNP: rs759900071
NCBI 1000 Genomes Browser:
rs759900071
Molecular consequence:
  • NM_000136.3:c.1069C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001243743.2:c.1069C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001243744.2:c.1069C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000566937GeneDxcriteria provided, single submitter
Pathogenic
(Apr 12, 2019)
germlineclinical testing

Citation Link,

SCV001551748Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedLikely pathogenicunknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000566937.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26740942)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001551748.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The FANCC p.Gln357X variant was identified in 1 of 56 proband chromosomes (frequency: 0.02) from individuals or families of Italian ethnicity with Fanconi anemia (Nicchia 2015); however, an insufficient number of controls were included in these studies to determine the frequency of this variant in the general population. The variant was also identified in dbSNP (ID: rs759900071) as “With Pathogenic allele”, and in the ClinVar and Clinvitae databases as pathogenic by GeneDx. The variant was not identified in Cosmic, MutDB and LOVD 3.0 databases or in the 1000 Genomes and NHLBI GO Exome Sequencing projects. The variant was identified in control databases in 1 of 246096 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include European Non-Finnish in 1 of 111662 chromosomes (freq: 0.00001), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, European Finnish, and South Asian populations. The c.1069C>T variant leads to a premature stop codon at position 357, which is predicted to lead to a truncated or absent protein, and loss of function. Loss of function variants of the FANCC gene are an established mechanism of disease in Fanconi anemia and is the type of variant expected to cause the disorder. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

Support Center