ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1827-1G>A (rs555449842)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471236 SCV000547774 pathogenic Fanconi anemia 2019-12-23 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 20 of the FANCA gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs555449842, ExAC 0.002%). This variant has been observed in several individuals affected with Fanconi anemia (PMID: 19367192, 29098742). ClinVar contains an entry for this variant (Variation ID: 408199). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). For these reasons, this variant has been classified as Pathogenic.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000667190 SCV000898674 pathogenic Fanconi anemia, complementation group A 2018-03-13 criteria provided, single submitter clinical testing FANCA NM_000135.3 exon 21 c.1827-1G>A: This variant has been reported in the literature in 5 individuals with Fanconi Anemia as homozygous or compound heterozygous (Moghrabi 2009 PMID:19367192). This variant is present in 7/124746 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs555449842). This variant is present in ClinVar (Variation ID:408199). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant alters the consensus splice sequence (+/- 1,2) which is predicted to result in an absent or abnormal protein. Loss of function variants are a known mechanism of disease for this gene (Mathew 2006 PMID:16998502). In summary, this variant is classified as pathogenic.
Counsyl RCV000667190 SCV000791606 pathogenic Fanconi anemia, complementation group A 2017-05-18 no assertion criteria provided clinical testing

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