Submissions for variant NM_022725.4(FANCF):c.633G>T (p.Gln211His)

gnomAD frequency: 0.00045  dbSNP: rs146975768

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000239026	SCV000297308	uncertain significance	not specified	2015-07-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001093961	SCV000370165	uncertain significance	Fanconi anemia complementation group F	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000320511	SCV000547716	uncertain significance	Fanconi anemia	2025-02-02	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 211 of the FANCF protein (p.Gln211His). This variant is present in population databases (rs146975768, gnomAD 0.05%). This missense change has been observed in individual(s) with FANCF-related condition (PMID: 33850299). ClinVar contains an entry for this variant (Variation ID: 252737). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FANCF protein function with a negative predictive value of 80%. 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001358441	SCV002011028	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000239026	SCV002066360	uncertain significance	not specified	2019-04-04	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000320511	SCV002530496	uncertain significance	Fanconi anemia	2021-09-29	criteria provided, single submitter	curation
GeneDx	RCV001358441	SCV002562428	uncertain significance	not provided	2022-11-11	criteria provided, single submitter	clinical testing	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: 29641532)
Fulgent Genetics, Fulgent Genetics	RCV001093961	SCV002816750	likely benign	Fanconi anemia complementation group F	2024-02-13	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358441	SCV001554175	uncertain significance	not provided		no assertion criteria provided	clinical testing