Submissions for variant NM_000136.3(FANCC):c.345+4AG[2]

dbSNP: rs755657969

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001080936	SCV000283590	likely benign	Fanconi anemia	2024-01-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000487298	SCV000564974	benign	not specified	2015-05-05	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.
Eurofins Ntd Llc (ga)	RCV000727370	SCV000707951	uncertain significance	not provided	2017-04-19	criteria provided, single submitter	clinical testing
Mendelics	RCV000988220	SCV001137857	uncertain significance	Fanconi anemia complementation group A	2019-05-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000727370	SCV004218676	uncertain significance	not provided	2022-10-10	criteria provided, single submitter	clinical testing	To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00016 (21/128724 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect FANCC mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355201	SCV001550015	uncertain significance	Fanconi anemia complementation group C		no assertion criteria provided	clinical testing	The FANCC c.345+8_345+9del variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (rs755657969) as “with other allele” and ClinVar (classified as benign by GeneDx, likely benign by Invitae and uncertain significance by EGL Genetic Diagnostics). The variant was identified in control databases in 25 of 281,798 chromosomes at a frequency of 0.00009 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 21 of 128,724 chromosomes (freq: 0.0002), African in 2 of 24,874 chromosomes (freq: 0.00008), and Latino in 2 of 35,296 chromosomes (freq: 0.00006), while it was not observed in the Ashkenazi Jewish, East Asian, Finnish, Other or South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Natera, Inc.	RCV001080936	SCV002081281	likely benign	Fanconi anemia	2018-04-11	no assertion criteria provided	clinical testing