Submissions for variant NM_000136.3(FANCC):c.1394A>G (p.Gln465Arg) (rs1800368)

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000120970	SCV000168413	benign	not specified	2014-01-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago	RCV000120970	SCV000247342	benign	not specified	2018-08-14	criteria provided, single submitter	clinical testing
Invitae	RCV001082312	SCV000252621	benign	Fanconi anemia	2019-12-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000574575	SCV000673295	likely benign	Hereditary cancer-predisposing syndrome	2018-12-05	criteria provided, single submitter	clinical testing	Other strong data supporting benign classification;In silico models in agreement (benign);Other data supporting benign classification
Integrated Genetics/Laboratory Corporation of America	RCV000590373	SCV000695425	benign	not provided	2016-04-29	criteria provided, single submitter	clinical testing	Variant summary: The c.1394A>G variant affects a non-conserved nucleotide, resulting in amino acid change from Gln to Arg. 5/5 in-silico tools predict benign outcome for this variant. This variant is found in 120/120326 control chromosomes at a frequency of 0.0009973, predominantly observed in African subpopulation in ExAC with observed MAF of 1%. This frequency exceeds the maximal expected frequency of a pathogenic allele (0.0017678), suggesting this variant is likely a benign polymorphism especially for Africans. This variant has been reported in the literature (Gibson_1996) in both cohorts of affected and control individuals and was classified by authors as a polymorphism. One patients unaffected parent who was obligated heterozygous carrier was genotyped to be homozygote for this variant, further supporting the neutral effect of this variant. In addition, multiple clinical laboratory/reputable database classified this variant as benign/likely benign, without evidence to independently evaluate. Taken together, the variant was classified as Benign.
Mendelics	RCV000988196	SCV001137833	likely benign	Fanconi anemia, complementation group A	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001169818	SCV001332595	likely benign	Fanconi anemia, complementation group C	2018-01-13	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ITMI	RCV000120970	SCV000085138	not provided	not specified	2013-09-19	no assertion provided	reference population
Leiden Open Variation Database	RCV000590373	SCV001365338	uncertain significance	not provided	2020-02-28	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.