ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.65G>A (p.Trp22Ter) (rs761341952)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665314 SCV000789413 pathogenic Fanconi anemia, complementation group A 2017-02-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000665314 SCV000915738 likely pathogenic Fanconi anemia, complementation group A 2017-04-28 criteria provided, single submitter clinical testing The FANCA c.65G>A (p.Trp22Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein. The p.Trp22Ter variant has been reported in at least three studies in which it is found in a total of five individuals with Fanconi anemia, including in two in a compound heterozygous state with a frameshift variant and in three in a heterozygous state without a second identified variant (Levran et al. 1997; Castella et al. 2011; De Rocco et al. 2014). The p.Trp22Ter variant was absent from four controls and is reported at a frequency of 0.00071 in the European (non-Finnish) population of the Exome Aggregation Consortium but this is based on two alleles only in a region of poor sequence coverage. Based on the evidence and the potential impact of stop-gained variants, the p.Trp22Ter variant is classified as likely pathogenic for Fanconi anemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000812393 SCV000952704 pathogenic Fanconi anemia 2018-10-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp22*) in the FANCA gene. It is expected to result in an absent or disrupted protein product. While this variant is present in population databases (rs761341952), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individuals and a family affected with Fanconi anemia (PMID: 9711872, 28717661, 29098742, 19367192,15643609). ClinVar contains an entry for this variant (Variation ID: 550541). Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). For these reasons, this variant has been classified as Pathogenic.
Molecular Diagnostics Laboratory,M Health: University of Minnesota RCV000665314 SCV000889964 pathogenic Fanconi anemia, complementation group A 2017-06-30 criteria provided, single submitter clinical testing

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