ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.2602-13CT[2]

dbSNP: rs577636020
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227314 SCV000283553 benign Fanconi anemia 2021-12-12 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000227314 SCV000399839 uncertain significance Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000858161 SCV001151105 likely pathogenic not provided 2019-02-01 criteria provided, single submitter clinical testing
Department of Pediatrics,Memorial Sloan Kettering Cancer Center RCV001523811 SCV001478120 likely pathogenic Fanconi anemia complementation group A 2020-12-15 criteria provided, single submitter research
GeneDx RCV000858161 SCV001764073 uncertain significance not provided 2020-03-05 criteria provided, single submitter clinical testing Variant detected in two families with Fanconi Anemia and was shown to lead to aberrant splicing by RT-PCR (Kimble 2018); In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing.; This variant is associated with the following publications: (PMID: 32235514, 29098742, 25589003)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000227314 SCV001821391 likely pathogenic Fanconi anemia 2021-08-26 criteria provided, single submitter clinical testing Variant summary: FANCA c.2602-9_2602-8delCT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, the variant has been shown to cause aberrant splicing in a patient derived cell line carrying the variant (Kimble_2018). The variant allele was found at a frequency of 0.00071 in 251154 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in FANCA causing Fanconi Anemia (0.00071 vs 0.0022), allowing no conclusion about variant significance. c.2602-9_2602-8delCT has been reported in the literature in individuals affected with Fanconi Anemia (Kimble_2018) and also in breast cancer patients (Bonache_2018, DelValle_2020, Schubert_2019). These data indicate that the variant may be associated with disease. Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=2), likely pathogenic (n=2) or benign (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000227314 SCV002032315 uncertain significance Fanconi anemia 2021-12-09 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800586 SCV002047088 likely benign not specified 2021-05-20 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV001800586 SCV002065233 uncertain significance not specified 2019-12-16 criteria provided, single submitter clinical testing DNA sequence analysis of the FANCA gene demonstrated a sequence change in intron 27, c.2602-9_2602-8del. This sequence change has been described in the gnomAD database with a frequency of 0.17% in European populations (dbSNP rs577636020). This sequence change, in addition to a large pathogenic deletion, has been identified in a Fanconi anemia family. RNA analysis of these individuals demonstrated skipping of exons 28-30 in the presence of this sequence change (PMID: 29098742). This sequence change is also predicted to have a deleterious effect on splicing based on in silico splice prediction programs. The functional significance of this sequence change is not known at present.

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