Submissions for variant NM_000136.3(FANCC):c.840G>A (p.Ser280=)

gnomAD frequency: 0.00154  dbSNP: rs34671520

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124966	SCV000168406	benign	not specified	2014-01-09	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000205819	SCV000260824	benign	Fanconi anemia	2025-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000565157	SCV000673299	likely benign	Hereditary cancer-predisposing syndrome	2016-11-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000124966	SCV000919325	benign	not specified	2018-11-30	criteria provided, single submitter	clinical testing	Variant summary: FANCC c.840G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00056 in 277166 control chromosomes, predominantly at a frequency of 0.0045 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 2.55 fold of the estimated maximal expected allele frequency for a pathogenic variant in FANCC causing Fanconi Anemia Group C phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.840G>A in individuals affected with Fanconi Anemia Group C and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Genetic Services Laboratory, University of Chicago	RCV000124966	SCV002070770	likely benign	not specified	2019-06-11	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000205819	SCV002535126	likely benign	Fanconi anemia	2021-02-04	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV003430691	SCV004160161	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	FANCC: BP4, BP7
Breakthrough Genomics, Breakthrough Genomics	RCV003430691	SCV005222438	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV000205819	SCV002081213	likely benign	Fanconi anemia	2017-05-10	no assertion criteria provided	clinical testing