ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.395C>G (p.Ala132Gly) (rs587779905)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000571052 SCV000673320 likely benign Hereditary cancer-predisposing syndrome 2017-11-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting benign classification,In silico models in agreement (benign)
GeneDx RCV000115352 SCV000149261 uncertain significance not provided 2018-01-28 criteria provided, single submitter clinical testing This variant is denoted FANCC c.395C>G at the cDNA level, p.Ala132Gly (A132G) at the protein level, and results in the change of an Alanine to a Glycine (GCT>GGT). This variant has been observed in an individual with prostate cancer (Lu 2015). FANCC Ala132Gly was not observed at a significant allele frequency in large population cohorts (Lek 2016). FANCC Ala132Gly is located in the regions of interaction with RED, FAZF, Hsp70 and GRP94 (Gordon 2000). In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether FANCC Ala132Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000315029 SCV000481137 uncertain significance Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000315029 SCV000549945 uncertain significance Fanconi anemia 2018-09-26 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 132 of the FANCC protein (p.Ala132Gly). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and glycine. This variant is present in population databases (rs587779905, ExAC 0.009%). This variant has not been reported in the literature in individuals with FANCC-related disease. ClinVar contains an entry for this variant (Variation ID: 127541). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000709093 SCV000838358 uncertain significance Fanconi anemia, complementation group C 2018-07-02 criteria provided, single submitter clinical testing

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