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

Total submissions: 6

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	likely benign	not specified	2015-04-28	criteria provided, single submitter	clinical testing
Invitae	RCV000198203	SCV000252621	benign	Fanconi anemia	2017-12-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000574575	SCV000673295	likely benign	Hereditary cancer-predisposing syndrome	2017-11-29	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: 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.
ITMI	RCV000120970	SCV000085138	not provided	not specified	2013-09-19	no assertion provided	reference population