ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.916G>A (p.Asp306Asn)

gnomAD frequency: 0.00001  dbSNP: rs772992002
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000559515 SCV000626264 uncertain significance Fanconi anemia 2022-10-02 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 306 of the FANCC protein (p.Asp306Asn). This variant is present in population databases (rs772992002, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 456173). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCC protein function. 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.
Ambry Genetics RCV001018955 SCV001180254 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-26 criteria provided, single submitter clinical testing The p.D306N variant (also known as c.916G>A), located in coding exon 9 of the FANCC gene, results from a G to A substitution at nucleotide position 916. The aspartic acid at codon 306 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478127 SCV004218699 uncertain significance not provided 2022-11-16 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.0000088 (1/113768 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In a large case-control study, the variant has been reported in one individual with breast cancer as well as in an unaffected control (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCC)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV001274470 SCV001458693 uncertain significance Fanconi anemia complementation group C 2020-09-16 no assertion criteria provided clinical testing

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