Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001066000 | SCV001230993 | pathogenic | Fanconi anemia | 2023-06-28 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 859808). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 15643609, 17924555). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs766643461, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 936 of the FANCA protein (p.Glu936Gly). 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 expected to disrupt FANCA protein function. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV002274132 | SCV002559505 | pathogenic | not provided | 2022-02-03 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect, with cell lines expressing the variant considered functionally null by both MMC cell viability and FANCD2 ubiquitylation assays (Karras et al., 2017); This variant is associated with the following publications: (PMID: 25525159, 31263571, 28215707, 17924555, 15643609) |
Rady Children's Institute for Genomic Medicine, |
RCV001066000 | SCV004046072 | pathogenic | Fanconi anemia | criteria provided, single submitter | clinical testing | This variant has been previously reported as a compound heterozygous change in patients with Fanconi anemia (PMID: 15643609, 17924555). Functional studies showed that this variant impaired the normal function of FANCA and also affected FANCA mRNA splicing (PMID: 17924555, 28215707). The c.2807A>G (p.Glu936Gly) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.006% (15/251486) and is absent in the homozygous state, thus is presumed to be rare. The c.2807A>G (p.Glu936Gly) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.2807A>G (p.Glu936Gly) variant is classified as Pathogenic. | |
Leiden Open Variation Database | RCV001256277 | SCV001425691 | pathogenic | Fanconi anemia complementation group A | 2020-02-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Johan de Winter. |