ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1279A>G (p.Met427Val)

gnomAD frequency: 0.00001  dbSNP: rs368103890
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001323812 SCV001514743 uncertain significance Fanconi anemia 2022-08-19 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 427 of the FANCA protein (p.Met427Val). This variant is present in population databases (rs368103890, gnomAD 0.005%). This missense change has been observed in individual(s) with pancreatic cancer (PMID: 28767289). ClinVar contains an entry for this variant (Variation ID: 1023721). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002291746 SCV002584619 uncertain significance Fanconi anemia complementation group A 2022-09-08 criteria provided, single submitter clinical testing The FANCA c.1279A>G (p.Met427Val) missense change has a maximum subpopulation frequency of 0.0044% in gnomAD v2.1.1 ( https://gnomad.broadinstitute.org/ ). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. This variant has been reported as heterozygous in an individual with duodenal adenocarcinoma (PMID: 28767289). To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Baylor Genetics RCV002291746 SCV004196052 uncertain significance Fanconi anemia complementation group A 2023-08-22 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478782 SCV004221910 uncertain significance not provided 2022-10-22 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000044 (5/113568 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with duodenal adenocarcinoma (PMID: 28767289 (2017)). 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. RCV001323812 SCV002095051 uncertain significance Fanconi anemia 2020-03-03 no assertion criteria provided clinical testing

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