Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002953289 | SCV003273495 | uncertain significance | Fanconi anemia | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with proline at codon 138 of the FANCG protein (p.Ala138Pro). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and proline. This variant is present in population databases (rs765854950, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with FANCG-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
St. |
RCV004786779 | SCV005402133 | uncertain significance | Fanconi anemia complementation group G | 2023-12-13 | criteria provided, single submitter | clinical testing | The FANCG c.412G>C (p.Ala138Pro) missense change has a maximum subpopulation frequency of 0.01% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Ambry Genetics | RCV004973751 | SCV005580651 | uncertain significance | Inborn genetic diseases | 2024-11-24 | criteria provided, single submitter | clinical testing | The p.A138P variant (also known as c.412G>C), located in coding exon 4 of the FANCG gene, results from a G to C substitution at nucleotide position 412. The alanine at codon 138 is replaced by proline, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |