Submissions for variant NM_000136.3(FANCC):c.202G>C (p.Gly68Arg)

gnomAD frequency: 0.00004  dbSNP: rs777111154

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206563	SCV000259780	uncertain significance	Fanconi anemia	2022-09-01	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 68 of the FANCC protein (p.Gly68Arg). This variant is present in population databases (rs777111154, gnomAD 0.02%). 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: 219736). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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	RCV001014138	SCV001174814	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-02	criteria provided, single submitter	clinical testing	The p.G68R variant (also known as c.202G>C), located in coding exon 2 of the FANCC gene, results from a G to C substitution at nucleotide position 202. The glycine at codon 68 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV001546776	SCV001766357	uncertain significance	not provided	2024-10-23	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on 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])
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV002291593	SCV002584719	uncertain significance	Fanconi anemia complementation group C	2022-06-20	criteria provided, single submitter	clinical testing	The FANCC c.202G>C (p.Gly68Arg) missense change has a maximum subpopulation frequency of 0.016% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the role of this variant in Fanconi anemia. It has therefore been classified as of uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV002291593	SCV002783111	uncertain significance	Fanconi anemia complementation group C	2021-12-07	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000206563	SCV002081297	uncertain significance	Fanconi anemia	2018-12-14	no assertion criteria provided	clinical testing