ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.4010+2T>C

dbSNP: rs2062067746
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV002250738 SCV002521766 pathogenic Fanconi anemia complementation group A 2022-05-22 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. This variant has been reported as uncertain significance (ClinVar ID: VCV000974064.1). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001256304 SCV002774277 likely pathogenic not provided 2021-07-23 criteria provided, single submitter clinical testing This variant is located in a canonical splice-donor site and is predicted to interfere with normal FANCA mRNA splicing. The variant has been reported in an individual with Fanconi Anemia (FA) in the published literature (PMID: 28717661 (2017)). Based on the available information, this variant is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003523083 SCV004296434 likely pathogenic Fanconi anemia 2023-11-17 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 40 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 individual(s) with Fanconi anemia (PMID: 28717661). ClinVar contains an entry for this variant (Variation ID: 974064). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Leiden Open Variation Database RCV001256304 SCV001425726 uncertain significance not provided 2020-02-28 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Daniela Pilonetto.

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