ClinVar Miner

Submissions for variant NM_001113378.2(FANCI):c.1573A>G (p.Met525Val)

gnomAD frequency: 0.00282  dbSNP: rs144908351
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228956 SCV000285883 benign Fanconi anemia 2024-01-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001094276 SCV000394198 likely benign Fanconi anemia complementation group I 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV000766508 SCV000574041 likely benign not provided 2020-07-14 criteria provided, single submitter clinical testing • Observed in cohorts of individuals with a personal and/or family history of cancer; however, several of these individuals also harbored variants in other cancer-related genes and the variant was also observed in control individuals (Cabanillas et al., 2017; Chandrasekharappa et al., 2017; Girard et al., 2019) • Observed with another FANCI variant of uncertain significance in internal GeneDx whole exome sequencing data in association with aplastic anemia and tongue cancer • In silico analysis supports that this missense variant does not alter protein structure/function • Observed in apparent homozygous state in multiple unrelated individuals in large population cohorts (Lek et al., 2016) and in a healthy adult individual tested at GeneDx • We interpret M525V as a likely benign variant
Genetic Services Laboratory, University of Chicago RCV000482252 SCV000594715 likely benign not specified 2021-01-08 criteria provided, single submitter clinical testing
Baylor Genetics RCV001094276 SCV001482733 uncertain significance Fanconi anemia complementation group I 2018-11-18 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000766508 SCV002011547 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000228956 SCV002529805 benign Fanconi anemia 2020-11-02 criteria provided, single submitter curation
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001094276 SCV003919934 likely benign Fanconi anemia complementation group I 2022-06-07 criteria provided, single submitter clinical testing This variant has not been reported in the literature in association with hematological disease. This variant is present in the Genome Aggregation Databse (Highest MAF: 0.4% [275/68032], 5 homozygotes https://gnomad.broadinstitute.org/variant/15-89281825-A-G?dataset=gnomad_r3). This variant is also present in ClinVar (Variation ID: 238309). Evoluationary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.
CeGaT Center for Human Genetics Tuebingen RCV000766508 SCV004137597 likely benign not provided 2024-02-01 criteria provided, single submitter clinical testing FANCI: BP4, BS2
PreventionGenetics, part of Exact Sciences RCV003955318 SCV004768042 likely benign FANCI-related disorder 2022-02-16 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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