ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.2497G>A (p.Asp833Asn)

gnomAD frequency: 0.00003  dbSNP: rs752560995
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000460410 SCV000547804 uncertain significance Fanconi anemia 2024-01-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 833 of the FANCM protein (p.Asp833Asn). This variant is present in population databases (rs752560995, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. ClinVar contains an entry for this variant (Variation ID: 408223). 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.
Fulgent Genetics, Fulgent Genetics RCV000763931 SCV000894875 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001785618 SCV002027874 uncertain significance not provided 2023-09-06 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 ovarian cancer (Dicks et al., 2017); This variant is associated with the following publications: (PMID: 28881617)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001785618 SCV004218743 uncertain significance not provided 2023-08-25 criteria provided, single submitter clinical testing In a large-scale breast cancer association study, the variant was observed in individuals with breast cancer as well unaffected individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/FANCM)). The frequency of this variant in the general population, 0.0014 (14/10086 chromosomes in Ashkenazi Jewish 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 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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