Submissions for variant NM_022725.4(FANCF):c.647G>C (p.Arg216Pro)

gnomAD frequency: 0.00022  dbSNP: rs192534185

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000499436	SCV000594700	uncertain significance	not specified	2016-01-13	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764966	SCV000896143	uncertain significance	Fanconi anemia complementation group F	2022-05-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001043635	SCV001207391	uncertain significance	Fanconi anemia	2022-10-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 216 of the FANCF protein (p.Arg216Pro). This variant is present in population databases (rs192534185, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with FANCF-related conditions. ClinVar contains an entry for this variant (Variation ID: 435150). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCF protein function. 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.
GeneDx	RCV001194789	SCV001992689	uncertain significance	not provided	2021-11-16	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001194789	SCV002011027	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Leiden Open Variation Database	RCV001194789	SCV001364578	uncertain significance	not provided	2019-09-30	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Andreas Laner.