Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001945719 | SCV002199576 | uncertain significance | Fanconi anemia | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with alanine at codon 3 of the FANCA protein (p.Asp3Ala). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and alanine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with FANCA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The alanine 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. |
| Ambry Genetics | RCV002558465 | SCV003658022 | uncertain significance | Inborn genetic diseases | 2022-12-01 | criteria provided, single submitter | clinical testing | The c.8A>C (p.D3A) alteration is located in exon 1 (coding exon 1) of the FANCA gene. This alteration results from a A to C substitution at nucleotide position 8, causing the aspartic acid (D) at amino acid position 3 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |