ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.874C>G (p.Pro292Ala)

gnomAD frequency: 0.00041  dbSNP: rs142747831
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812167 SCV000952471 uncertain significance Fanconi anemia 2024-01-30 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 292 of the FANCM protein (p.Pro292Ala). This variant is present in population databases (rs142747831, gnomAD 0.1%). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 26740942). ClinVar contains an entry for this variant (Variation ID: 655897). 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 tolerated. 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 RCV001551936 SCV001772544 uncertain significance not provided 2023-08-08 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed with FANCM p.Leu1950Val (phase unknown) in an individual with Fanconi anemia who was also heterozygous for a nonsense variant in the FANCA gene (Nicchia et al., 2015); This variant is associated with the following publications: (PMID: 26740942)
Fulgent Genetics, Fulgent Genetics RCV002495133 SCV002779043 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2022-03-16 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001551936 SCV004218848 uncertain significance not provided 2023-06-19 criteria provided, single submitter clinical testing In the published literature, this variant has been reported in an individual with Fanconi anemia (PMID: 26740942 (2015)). The frequency of this variant in the general population, 0.0014 (34/24950 chromosomes in African/African American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. 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.

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