ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.5791C>T (p.Arg1931Ter) (rs144567652)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000722040 SCV000853217 pathogenic Malignant germ cell tumor of ovary 2018-06-12 criteria provided, single submitter clinical testing This is a nonsense alteration in which a C is replaced by a T at coding nucleotide 5791 and is predicted to change an Arginine to a premature stop codon at amino acid codon 1931. Classification criteria: PVS1, PS3.
Invitae RCV000630904 SCV000751877 uncertain significance Fanconi anemia 2019-01-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1931*) in the FANCM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs144567652, ExAC 0.5%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in case-control studies as a potential breast cancer risk factor, though the statistical significance of these findings is uncertain [OR = 2.29; 95%CI = 0.71–8.54; P = 0.13]; [OR = 3.93; 95% CI = 1.28–12.11; P = 0.017] (PMID: 23409019, 26130695). In another case-control study for male breast cancer, this variant was only observed in unaffected male controls (PMID: 29287190). In addition, this variant has been observed as homozygous in an individual with no reported symptoms of Fanconi anemia (PMID: 25078778). Experimental studies have shown that this sequence change results in the skipping of exon 22 and an exon 22 deletion variant could not rescue mitomycin C sensitivity or diepoxybutane-induced chromosome fragility phenotype in a FANCM-deficient mouse fibroblast line (PMID: 26130695). The clinical significance of these results is uncertain. 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.
OMIM RCV000677277 SCV000803410 pathogenic SPERMATOGENIC FAILURE 28 2018-08-14 no assertion criteria provided literature only

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