ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.3877G>A (p.Glu1293Lys)

dbSNP: rs1015729981
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001822688 SCV002071891 uncertain significance not specified 2021-10-01 criteria provided, single submitter clinical testing DNA sequence analysis of the FANCA gene demonstrated a sequence change, c.3877G>A, in exon 39 that results in an amino acid change, p.Glu1293Lys. This sequence change does not appear to have been previously described in individuals with FANCA-related disorders and has also not been described in the population databases such as ExAC and gnomAD (dbSNP rs1015729981). The p.Glu1293Lys change affects a poorly conserved amino acid residue located in a domain of the FANCA protein that is known to be functional. The p.Glu1293Lys substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Glu1293Lys change remains unknown at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV002542678 SCV002958412 uncertain significance Fanconi anemia 2022-10-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1293 of the FANCA protein (p.Glu1293Lys). This variant is not present in population databases (gnomAD no frequency). 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: 1338090). 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. 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.

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