ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.2842G>C (p.Asp948His)

gnomAD frequency: 0.00011  dbSNP: rs778254482
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001366149 SCV001562443 uncertain significance Fanconi anemia 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 948 of the FANCA protein (p.Asp948His). This variant is present in population databases (rs778254482, gnomAD 0.004%). 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: 1057210). 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.
Sema4, Sema4 RCV001366149 SCV002534973 uncertain significance Fanconi anemia 2022-03-17 criteria provided, single submitter curation
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003478797 SCV004221983 uncertain significance not provided 2024-02-02 criteria provided, single submitter clinical testing The FANCA c.2842G>C (p.Asp948His) variant has not been reported in individuals with FANCA-related conditions in the published literature. The frequency of this variant in the general population, 0.0000071 (2/282876 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Ambry Genetics RCV004036964 SCV004869461 uncertain significance Inborn genetic diseases 2024-11-18 criteria provided, single submitter clinical testing The p.D948H variant (also known as c.2842G>C), located in coding exon 29 of the FANCA gene, results from a G to C substitution at nucleotide position 2842. The aspartic acid at codon 948 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005014496 SCV005644438 uncertain significance Fanconi anemia complementation group A 2024-04-30 criteria provided, single submitter clinical testing
Natera, Inc. RCV001366149 SCV002092575 uncertain significance Fanconi anemia 2020-01-17 no assertion criteria provided clinical testing

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