Submissions for variant NM_000136.3(FANCC):c.800A>G (p.Asn267Ser)

gnomAD frequency: 0.00005  dbSNP: rs200854639

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000160479	SCV000211044	uncertain significance	not provided	2023-04-11	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: Gordon2000[Book])
Invitae	RCV000233995	SCV000283598	uncertain significance	Fanconi anemia	2021-11-24	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 267 of the FANCC protein (p.Asn267Ser). This variant is present in population databases (rs200854639, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 182478). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV000562231	SCV000673327	uncertain significance	Hereditary cancer-predisposing syndrome	2021-11-18	criteria provided, single submitter	clinical testing	The p.N267S variant (also known as c.800A>G), located in coding exon 7 of the FANCC gene, results from an A to G substitution at nucleotide position 800. The asparagine at codon 267 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV001274478	SCV002778793	uncertain significance	Fanconi anemia complementation group C	2021-10-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000160479	SCV004218692	uncertain significance	not provided	2023-05-17	criteria provided, single submitter	clinical testing	In a large-scale breast cancer association study, the variant was observed in breast cancer cases and in unaffected individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCC)). The frequency of this variant in the general population, 0.000059 (3/50804 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc.	RCV001274478	SCV001458701	uncertain significance	Fanconi anemia complementation group C	2020-09-16	no assertion criteria provided	clinical testing