ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1734_1739del (p.Tyr578_Val580delinsTer)

gnomAD frequency: 0.00001  dbSNP: rs757504102
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669747 SCV000794528 likely pathogenic Fanconi anemia complementation group A 2017-09-28 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV000669747 SCV001762384 pathogenic Fanconi anemia complementation group A 2021-06-21 criteria provided, single submitter clinical testing FANCA c.1734_1739del (rs1400163791) is rare (<0.1%) in a large population dataset (gnomAD: 2/251378 total alleles; 0.0008%; no homozygotes) and has been reported in ClinVar(Variation ID: 554168). It has not been reported in the literature to our knowledge. This multi-nucleotide deletion results in a premature stop codon in exon 19 likely leading to nonsense-mediated decay and lack of protein production. We consider FANCA c.1734_1739del to be pathogenic.
Invitae RCV001861781 SCV002122473 pathogenic Fanconi anemia 2022-12-13 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: 554168). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 29098742). This variant is present in population databases (rs757504102, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Tyr578*) in the FANCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192).
GeneDx RCV002253554 SCV002525289 likely pathogenic not provided 2022-05-25 criteria provided, single submitter clinical testing Identified in two unrelated individuals with Fanconi anemia with a second variant, however, phase of both sets of variants is unknown (Kimble et al., 2018); Nonsense variant predicted to result in protein truncation or nonsense mediated decay 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: 29098742)

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