ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.6041T>C (p.Val2014Ala)

gnomAD frequency: 0.00006  dbSNP: rs374376462
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001238162 SCV001410961 uncertain significance Fanconi anemia 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2014 of the FANCM protein (p.Val2014Ala). This variant is present in population databases (rs374376462, gnomAD 0.009%). This missense change has been observed in individual(s) with head and neck squamous cell carcinoma (PMID: 28678401). ClinVar contains an entry for this variant (Variation ID: 964025). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
GeneDx RCV003156324 SCV003845577 uncertain significance not provided 2023-03-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with head and neck cancer (Chandrasekharappa et al., 2017); This variant is associated with the following publications: (PMID: 28678401)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003156324 SCV004218838 uncertain significance not provided 2023-04-20 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000085 (11/128958 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual affected with head and neck squamous cell carcinoma (PMID: 28678401 (2017)), as well as in cases and a control individual in a large scale breast cancer association study (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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