Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001241327 | SCV001414339 | uncertain significance | Fanconi anemia | 2022-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1128 of the FANCA protein (p.Gln1128Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 9371798). ClinVar contains an entry for this variant (Variation ID: 551847). 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. Experimental studies have shown that this missense change affects FANCA function (PMID: 16946016, 30057198). 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. |
Myriad Genetics, |
RCV000667004 | SCV002060257 | uncertain significance | Fanconi anemia complementation group A | 2021-11-08 | criteria provided, single submitter | clinical testing | NM_000135.2(FANCA):c.3382C>G(Q1128E) is a missense variant classified as a variant of uncertain significance in the context of Fanconi anemia complementation group A. Q1128E has been observed in cases with relevant disease (PMID: 9371798). Functional assessments of this variant are available in the literature (PMID: 30057198, 12444097, 16946016). Q1128E has not been observed in population frequency databases. In summary, there is insufficient evidence to classify NM_000135.2(FANCA):c.3382C>G(Q1128E) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Leiden Open Variation Database | RCV000667004 | SCV001425705 | pathogenic | Fanconi anemia complementation group A | 2020-02-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. |
Natera, |
RCV001241327 | SCV002092533 | uncertain significance | Fanconi anemia | 2021-01-20 | no assertion criteria provided | clinical testing |