ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1827-2A>G

dbSNP: rs2143393518
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237526 SCV002010198 pathogenic not provided 2021-11-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002544206 SCV003481305 pathogenic Fanconi anemia 2024-01-25 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. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Fanconi anemia (PMID: 19367192). ClinVar contains an entry for this variant (Variation ID: 1319527). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003325232 SCV004031134 likely pathogenic Fanconi anemia complementation group A 2023-08-17 criteria provided, single submitter clinical testing The FANCA c.1827-2A>G intronic change results in an A to G substitution at the -2 position of intron 20 of the FANCA gene. This variant is predicted to result in loss of the native splice acceptor site and may result in the use of a cryptic acceptor site. This change is predicted to cause protein truncation or absence of protein due to nonsense-mediated decay. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. This variant is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as likely pathogenic. 
Baylor Genetics RCV003325232 SCV004196642 likely pathogenic Fanconi anemia complementation group A 2022-03-12 criteria provided, single submitter clinical testing

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