ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.775C>G (p.Pro259Ala)

dbSNP: rs200988394
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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 RCV001059113 SCV001223722 uncertain significance Fanconi anemia 2022-07-11 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 259 of the FANCA protein (p.Pro259Ala). This variant is present in population databases (rs200988394, gnomAD 0.004%). This missense change has been observed in individual(s) with T-cell acute lymphoblastic leukemia (PMID: 31721781). ClinVar contains an entry for this variant (Variation ID: 854140). 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. Experimental studies have shown that this missense change affects FANCA function (PMID: 31721781). 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 RCV001800947 SCV002046912 uncertain significance not specified 2021-04-14 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001059113 SCV002535074 uncertain significance Fanconi anemia 2021-04-07 criteria provided, single submitter curation
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001274648 SCV005689052 uncertain significance Fanconi anemia complementation group A 2024-08-22 criteria provided, single submitter clinical testing The FANCA c.775C>G (p.Pro259Ala) missense change has a maximum subpopulation frequency of 0.005% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function. 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.
Natera, Inc. RCV001274648 SCV001459002 uncertain significance Fanconi anemia complementation group A 2020-09-16 no assertion criteria provided clinical testing

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