ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.1414G>A (p.Gly472Arg)

gnomAD frequency: 0.00002  dbSNP: rs201063698
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205771 SCV000259293 likely benign Fanconi anemia 2024-01-28 criteria provided, single submitter clinical testing
GeneDx RCV001310662 SCV000278974 likely benign not provided 2020-10-13 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24728327, 21279724, 28767289)
Ambry Genetics RCV001011455 SCV001171777 benign Hereditary cancer-predisposing syndrome 2023-04-03 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: 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.
CeGaT Center for Human Genetics Tuebingen RCV001310662 SCV001500549 likely benign not provided 2020-10-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001509574 SCV001716360 likely benign Fanconi anemia complementation group C 2021-05-18 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000205771 SCV002535090 uncertain significance Fanconi anemia 2021-08-05 criteria provided, single submitter curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000120972 SCV004122043 likely benign not specified 2023-10-24 criteria provided, single submitter clinical testing Variant summary: FANCC c.1414G>A (p.Gly472Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 251292 control chromosomes, predominantly at a frequency of 0.0025 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.4 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 South Asian origin. c.1414G>A has been reported in the literature in individuals affected with Pancreas cancer (example, Bhai_2021, Shindo_2017), without strong evidence for causality. These report(s) do not provide unequivocal conclusions about association of the variant with Fanconi Anemia Group C or other FANCC related diseases. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34326862, 28767289). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 (Likely benign, n=4, Benign, n=1, VUS, n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001310662 SCV004218668 likely benign not provided 2023-03-23 criteria provided, single submitter clinical testing
ITMI RCV000120972 SCV000085140 not provided not specified 2013-09-19 no assertion provided reference population

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