Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostics Laboratory, |
RCV000665314 | SCV000889964 | pathogenic | Fanconi anemia complementation group A | 2017-06-30 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
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 | 2024-01-24 | 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. Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). This variant is present in population databases (rs761341952, gnomAD 0.2%). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 9711872, 15643609, 19367192, 28717661, 29098742). ClinVar contains an entry for this variant (Variation ID: 550541). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV000665314 | SCV001194122 | pathogenic | Fanconi anemia complementation group A | 2020-01-03 | criteria provided, single submitter | clinical testing | NM_000135.2(FANCA):c.65G>A(W22*) is classified as pathogenic in the context of Fanconi anemia. Sources cited for classification include the following: PMID 15643609, 19367192 and 29098742. Classification of NM_000135.2(FANCA):c.65G>A(W22*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening. |
Mayo Clinic Laboratories, |
RCV001509539 | SCV001716295 | pathogenic | not provided | 2020-08-21 | criteria provided, single submitter | clinical testing | PVS1, PS1, PS4, PM2 |
Genetic Services Laboratory, |
RCV001509539 | SCV002070495 | pathogenic | not provided | 2020-07-14 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the FANCA gene demonstrated a base pair change, c.65G>A, which results in the creation of a premature stop codon at amino acid residue 22, p.Trp22*. This sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated FANCA protein with potentially abnormal function. The p.Trp22* change has been described in several individuals with a clinical diagnosis of Fanconi anemia (PMIDs: 9371798, 29098742); both in the homozygous (PMID: 31558676) and compound heterozgyous state (PMIDs: 31558676, 9711872, 19367192). This sequence change is present in the gnomAD database with a frequency of 0.17% in the Ashkenzi Jewish sub-population (dbSNP rs761341952). These collective evidences indicate that this sequence change is pathogenic, however functional studies have not been performed to prove this conclusively. |
Sema4, |
RCV000812393 | SCV002535063 | pathogenic | Fanconi anemia | 2021-04-27 | criteria provided, single submitter | curation | |
Fulgent Genetics, |
RCV000665314 | SCV002804264 | pathogenic | Fanconi anemia complementation group A | 2022-02-13 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000665314 | SCV004195986 | pathogenic | Fanconi anemia complementation group A | 2023-10-28 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001509539 | SCV004218637 | pathogenic | not provided | 2022-01-25 | criteria provided, single submitter | clinical testing | This nonsense variant causes the premature termination of FANCA protein synthesis. The frequency of this variant in the general population, 0.0017 (6/3470 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with Fanconi anemia, complementation group A, and is considered an Ashkenazi Jewish founder mutation (PMIDs: 29098742 (2018), 24584348 (2014), 21273304 (2011), 19367192 (2009), 15643609 (2005), 9371798 (1997)). Based on the available information, this variant is classified as pathogenic. |
Leiden Open Variation Database | RCV000665314 | SCV001426010 | pathogenic | Fanconi anemia complementation group A | 2020-02-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. |
Natera, |
RCV000665314 | SCV001459019 | pathogenic | Fanconi anemia complementation group A | 2020-09-16 | no assertion criteria provided | clinical testing |