Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Fulgent Genetics, |
RCV002493817 | SCV002780706 | uncertain significance | Fanconi anemia complementation group A | 2022-04-06 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002547601 | SCV003453385 | uncertain significance | Fanconi anemia | 2022-05-20 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 7 of the FANCA protein (p.Pro7Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with FANCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1049198). 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. 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. |
| Department of Pathology and Laboratory Medicine, |
RCV001354987 | SCV001549733 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The FANCA p.Pro7Gln variant was not identified in the literature nor was it identified in the ClinVar, Cosmic, MutDB or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs772712346). The variant was identified in control databases in 3 of 154722 chromosomes at a frequency of 0.000019 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 4770 chromosomes (freq: 0.00021) and South Asian in 2 of 21316 chromosomes (freq: 0.000094), but not in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish) and European (non-Finnish) populations. The p.Pro7 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |