ClinVar Miner

Submissions for variant NM_022725.3(FANCF):c.480_481CT[2] (p.Leu162fs) (rs587778340)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ITMI RCV000121020 SCV000085188 not provided not specified 2013-09-19 no assertion provided reference population
Illumina Clinical Services Laboratory,Illumina RCV000006715 SCV000370168 pathogenic Fanconi anemia, complementation group F 2017-04-28 criteria provided, single submitter clinical testing The FANCF c.484_485delCT (p.Leu162AspfsTer103) variant results in a frameshift, and is predicted to cause premature termination of the protein. The p.Leu162AspfsTer103 variant has been reported in three studies in which it is found in a total of six patients with Fanconi anemia including in four in homozygous state (including three sibling fetuses terminated for congenital anomalies), and in two in a compound heterozygous state (de Winter et al. 2000; Nicchia et al. 2015; Chandra et al. 2005). Control data are unavailable for this variant, which is reported at a frequency of 0.00024 in the South Asian population of the Exome Aggregation Consortium. The FANCF protein was absent in lymphoblasts from an individual who was homozygous for the variant (de Winter et al. 2000). Due to the potential impact of frameshift variants and the collective evidence, the p.Leu162AspfsTer103 variant is classified as pathogenic for Fanconi anemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000820044 SCV000960736 pathogenic Fanconi anemia 2018-12-10 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the FANCF gene (p.Leu162Aspfs*103). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 213 amino acids of the FANCF protein. This variant is present in population databases (rs587778340, ExAC 0.02%). This variant has been observed to be homozygous or in combination with another pathogenic FANCF variant in individuals affected with Fanconi anemia (FA) (PMID: 26033879, 28102861, 27714961). ClinVar contains an entry for this variant (Variation ID: 6343). Experimental studies of cells isolated from a FA-patient have shown that this change in the homozygous state disrupts protein expression (PMID: 10615118). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000006715 SCV000026906 pathogenic Fanconi anemia, complementation group F 2000-01-01 no assertion criteria provided literature only

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