Submissions for variant NM_000136.3(FANCC):c.672C>T (p.Asn224=)

gnomAD frequency: 0.00046  dbSNP: rs150647141

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124963	SCV000168403	benign	not specified	2014-02-20	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	RCV000227447	SCV000283596	likely benign	Fanconi anemia	2024-01-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000566669	SCV000673302	likely benign	Hereditary cancer-predisposing syndrome	2017-08-01	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	RCV000124963	SCV000917331	likely benign	not specified	2019-08-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001165846	SCV001328094	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Sema4, Sema4	RCV000227447	SCV002535117	likely benign	Fanconi anemia	2021-03-05	criteria provided, single submitter	curation
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356398	SCV001551556	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The FANCC p.Asn224= variant was not identified in the literature nor was it identified in the LOVD 3.0, databases. The variant was identified in dbSNP (ID: rs150647141) as With Likely benign allele, ClinVar (classified as benign by GeneDx; classified as likely benign by Invitae), Clinvitae (classified as benign by ClinVar; classified as likely benign by Invitae), databases. The variant was identified in control databases in 35 of 263702 chromosomes at a frequency of 0.000133 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). The p.Asn224= 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. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) 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.
References (PMIDs): N/A
Natera, Inc.	RCV000227447	SCV002081233	likely benign	Fanconi anemia	2018-04-25	no assertion criteria provided	clinical testing