ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.5569G>A (p.Val1857Met)

gnomAD frequency: 0.00049  dbSNP: rs144008013
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000465642 SCV000547802 uncertain significance Fanconi anemia 2022-10-28 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1857 of the FANCM protein (p.Val1857Met). This variant is present in population databases (rs144008013, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with breast cancer (PMID: 19737859). ClinVar contains an entry for this variant (Variation ID: 408221). 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: "Probably Damaging"; 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.
Fulgent Genetics, Fulgent Genetics RCV000765164 SCV000896393 uncertain significance Spermatogenic failure 28; Premature ovarian failure 15 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001662428 SCV001875099 uncertain significance not provided 2023-11-06 criteria provided, single submitter clinical testing Observed in individuals with a personal and/or family history of breast cancer but also in unaffected controls (PMID: 19737859, 33471991, 35802266); Observed in an individual with cervical cancer and papillary urothelial carcinoma who also had a germline pathogenic variant identified in VHL (PMID: 34628056); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33471991, 26596371, 35802266, 19737859, 34628056, 37656691, 34326862)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV001662428 SCV002011469 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002255393 SCV002529883 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-19 criteria provided, single submitter curation
GenomeConnect, ClinGen RCV000709952 SCV000840312 not provided Fanconi anemia, complementation group M no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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