ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.3382C>G (p.Gln1128Glu)

gnomAD frequency: 0.00001  dbSNP: rs1439817346
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Total submissions: 4
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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, Inc. 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, Inc. RCV001241327 SCV002092533 uncertain significance Fanconi anemia 2021-01-20 no assertion criteria provided clinical testing

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