Submissions for variant NM_000136.3(FANCC):c.1485G>A (p.Leu495=)

dbSNP: rs56082100

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124975	SCV000168415	benign	not specified	2014-02-05	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.
Invitae	RCV000205120	SCV000261502	benign	Fanconi anemia	2024-01-31	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000124975	SCV000345076	likely benign	not specified	2016-08-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567268	SCV000673305	likely benign	Hereditary cancer-predisposing syndrome	2017-08-19	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.
Illumina Laboratory Services, Illumina	RCV001167959	SCV001330510	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000124975	SCV002511387	likely benign	not specified	2022-04-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000205120	SCV002535092	likely benign	Fanconi anemia	2021-02-03	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000124975	SCV002774545	benign	not specified	2021-07-16	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001167959	SCV002806479	likely benign	Fanconi anemia complementation group C	2021-07-29	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001167959	SCV004017618	benign	Fanconi anemia complementation group C	2023-07-07	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356823	SCV001552092	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The FANCC p.Leu495= variant was not identified in the literature nor was it identified in the LOVD 3.0 database. The variant was identified in dbSNP (rs56082100) as “with likely benign, other allele” and ClinVar (classified as benign by Invitae and GeneDx; and as likely benign by Ambry Genetics and Eurofins). The variant was identified in control databases in 161 of 282,768 chromosomes at a frequency of 0.0006 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 153 of 24,950 chromosomes (freq: 0.006), Latino in 7 of 35,438 chromosomes (freq: 0.0002), and Other in 1 of 7220 chromosomes (freq: 0.0001); it was not observed in the Ashkenazi Jewish, East Asian, Finnish, European or South Asian populations. The p.Leu495= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-highly conserved nucleotide 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 although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Natera, Inc.	RCV000205120	SCV002081144	likely benign	Fanconi anemia	2018-04-10	no assertion criteria provided	clinical testing