Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000671893 | SCV000796926 | likely pathogenic | Fanconi anemia complementation group A | 2018-01-04 | criteria provided, single submitter | clinical testing | |
Molecular Diagnostics Laboratory, |
RCV000671893 | SCV000891230 | likely pathogenic | Fanconi anemia complementation group A | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000796523 | SCV000936041 | pathogenic | Fanconi anemia | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 913 of the FANCA protein (p.His913Pro). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individuals with Fanconi anemia (PMID: 29098742, 29269525). ClinVar contains an entry for this variant (Variation ID: 555969). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCA protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects FANCA function (PMID: 29269525). For these reasons, this variant has been classified as Pathogenic. |
Genetic Services Laboratory, |
RCV001816676 | SCV002064667 | pathogenic | not provided | 2019-07-12 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the FANCA gene demonstrated a sequence change, c.2621G>C in exon 28, which results in an amino acid change, p.Arg874Thr. The p.Arg874Thr change affects a highly conserved amino acid residue located in a domain of the FANCA protein that is not known to be functional. The p.Arg874Thr substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, CADD, REVEL, in silico splice prediction programs). This sequence change is absent from large population databases such as ExAC and gnomAD. The p.Arg874Thr amino acid change occurs in a region of the FANCA gene where other missense sequence changes have been described in patients with FANCA-related disorders (PMIDs: 15643609, 24116929). This sequence change was identified with another likely pathogenic FANCA variant in a patient. |
Fulgent Genetics, |
RCV000671893 | SCV002801433 | likely pathogenic | Fanconi anemia complementation group A | 2021-12-24 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000671893 | SCV004196595 | pathogenic | Fanconi anemia complementation group A | 2023-01-17 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000671893 | SCV001737413 | not provided | Fanconi anemia complementation group A | no assertion provided | literature only | Associated with slower hematologic disease progression |