ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.3348+1G>A

dbSNP: rs751266148
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668641 SCV000793275 pathogenic Fanconi anemia complementation group A 2017-08-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001246767 SCV001420149 pathogenic Fanconi anemia 2023-12-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 33 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 present in population databases (rs751266148, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with Fanconi anemia (PMID: 23613520, 24584348). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 553239). 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.
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV001270082 SCV001448875 pathogenic not provided 2017-08-04 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003420183 SCV004117258 pathogenic FANCA-related disorder 2023-05-17 criteria provided, single submitter clinical testing The FANCA c.3348+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in multiple individuals with Fanconi anemia (Chandrasekharappa et al 2013. PubMed ID: 23613520, Table 1; Nia et al 2016. PubMed ID: 27041517, Table 2; De Rocco et al 2014. PubMed ID: 24584348, Table 1). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-89815066-C-T). This variant is predicted to disrupt a consensus splice donor site (Alamut Visual Plus v1.6.1). Variants that disrupt the consensus splice donor site in FANCA are expected to be pathogenic. This variant is interpreted as pathogenic.

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