Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672136 | SCV000797203 | likely pathogenic | Fanconi anemia complementation group A | 2018-01-16 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797781 | SCV002041885 | pathogenic | Fanconi anemia | 2021-11-04 | criteria provided, single submitter | clinical testing | Variant summary: FANCA c.2303T>C (p.Leu768Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.5e-06 in 210674 control chromosomes. c.2303T>C has been reported in the literature as homozygous and compound heterozygous genotypes in multiple individuals affected with Fanconi Anemia (example, Levran_2005, Moghrabi_2009, Castella_2011, Gille_2012, Galvez_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory and a database (LOVD) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Invitae | RCV001797781 | SCV002139087 | uncertain significance | Fanconi anemia | 2022-03-21 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 768 of the FANCA protein (p.Leu768Pro). 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 missense change has been observed in individuals with Fanconi anemia, and breast cancer (PMID: 15643609, 19367192, 21273304, 22778927, 32235514). ClinVar contains an entry for this variant (Variation ID: 556171). 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. 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. |
| Baylor Genetics | RCV000672136 | SCV004196006 | likely pathogenic | Fanconi anemia complementation group A | 2023-10-11 | criteria provided, single submitter | clinical testing | |
| Leiden Open Variation Database | RCV000672136 | SCV001425675 | 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. |