ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.3934+2T>C

dbSNP: rs771775516
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669249 SCV000793983 likely pathogenic Fanconi anemia complementation group A 2017-09-06 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000669249 SCV002073175 pathogenic Fanconi anemia complementation group A criteria provided, single submitter clinical testing The splice donor variant c.3934+2T>C in FANCA (NM_000135.4) has been reported to ClinVar as Likely Pathogenic. The c.3934+2T>C variant is observed in 1/30,616 (0.0033%) alleles from individuals of South Asian background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant mutates a splice-donor sequence, potentially resulting in the retention of large segments of intronic DNA by the mRNA and nonfunctional proteins. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000669249 SCV004196091 pathogenic Fanconi anemia complementation group A 2024-01-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003767972 SCV004623164 pathogenic Fanconi anemia 2023-04-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 553736). Disruption of this splice site has been observed in individuals with Fanconi anemia (PMID: 15523645, 29098742, 34585473). This variant is present in population databases (rs771775516, gnomAD 0.003%). This sequence change affects a donor splice site in intron 39 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).
GeneDx RCV004702288 SCV005201765 pathogenic not provided 2024-01-25 criteria provided, single submitter clinical testing Observed multiple times with another FANCA variant in unrelated patients in published literature with Fanconi anemia, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes in all cases (PMID: 29098742, 15523645); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15523645, 25525159, 34585473, 35955545, 35929646, 29098742)
Fulgent Genetics, Fulgent Genetics RCV000669249 SCV005642578 pathogenic Fanconi anemia complementation group A 2024-02-21 criteria provided, single submitter clinical testing

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