ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.839C>T (p.Ala280Val)

gnomAD frequency: 0.00001  dbSNP: rs767092317
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673713 SCV000798948 uncertain significance Fanconi anemia complementation group A 2018-03-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001058370 SCV001222934 uncertain significance Fanconi anemia 2022-07-09 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 280 of the FANCA protein (p.Ala280Val). This variant is present in population databases (rs767092317, gnomAD 0.007%). 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: 557556). 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 FANCA 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478398 SCV004218647 uncertain significance not provided 2023-04-21 criteria provided, single submitter clinical testing In the published literature, the variant has been reported in an individual with head and neck squamous cell carcinoma (PMID: 28678401 (2017)) and an individual with ovarian cancer (PMID: 32546565 (2021)). The frequency of this variant in the general population, 0.000008 (2/250206 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. 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.
Natera, Inc. RCV001058370 SCV002095094 uncertain significance Fanconi anemia 2020-07-13 no assertion criteria provided clinical testing

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