Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001046724 | SCV001210638 | uncertain significance | Fanconi anemia | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glycine at codon 257 of the FANCG protein (p.Arg257Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with FANCG-related conditions (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Genomic Medicine Center of Excellence, |
RCV001283830 | SCV004806135 | likely pathogenic | Fanconi anemia complementation group G | 2024-03-25 | criteria provided, single submitter | clinical testing | |
| Human Genetics Section, |
RCV001283830 | SCV005077819 | likely pathogenic | Fanconi anemia complementation group G | 2024-07-11 | criteria provided, single submitter | research | The variant p.Arg257Gly in FANCG was found in an individual affected with fanconi anemia, absent in large population studies. The classification was taken from https://franklin.genoox.com/clinical-db/variant/snp/chr9-35076976-G-C Clarification (July 23, 2024): Franklin and Varsome were utilized as supplementary tools; however, the patient was diagnosed with Fanconi anemia by a hematologist. Predictive tools indicated that the variant was possibly damaging according to SIFT, damaging according to PolyPhen, and had a CADD score of 25.7. The bone marrow biopsy revealed mildly megaloblastic maturation with no significant dysplasia. Clinical features included café-au-lait spots, short stature, and growth retardation (failure to thrive). Whole Genome Sequencing (WGS) identified a variant explaining the observed phenotypes. We are currently preparing a publication detailing these findings, and the PubMed ID (PMID) will be provided upon release. |
| Biochemical Molecular Genetic Laboratory, |
RCV001283830 | SCV001469250 | uncertain significance | Fanconi anemia complementation group G | 2021-09-06 | no assertion criteria provided | clinical testing |